{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:05:12Z","timestamp":1788869112740,"version":"build-2803163510"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006687","name":"Lyon 1 University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-18-CE12-0007-01"],"award-info":[{"award-number":["ANR-18-CE12-0007-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Various genetic diseases associated with microcephaly and developmental defects are due to pathogenic variants in the U4atac small nuclear RNA (snRNA), a component of the minor spliceosome essential for the removal of U12-type introns from eukaryotic mRNAs. While it has been shown that a few RNU4ATAC mutations result in impaired binding of essential protein components, the molecular defects of the vast majority of variants are still unknown. Here, we used lymphoblastoid cells derived from RNU4ATAC compound heterozygous (g.108_126del;g.111G&amp;gt;A) twin patients with MOPD1 phenotypes to analyze the molecular consequences of the mutations on small nuclear ribonucleoproteins (snRNPs)\u00a0formation and on splicing. We found that the U4atac108_126del mutant is unstable and that the U4atac111G&amp;gt;A mutant as well as the minor di- and tri-snRNPs are present at reduced levels. Our results also reveal the existence of 3\u2019-extended snRNA transcripts in patients\u2019 cells. Moreover, we show that the mutant cells have alterations in splicing of INTS7 and INTS10 minor introns, contain lower levels of the INTS7 and INTS10 proteins and display changes in the assembly of Integrator subunits. Altogether, our results show that compound heterozygous g.108_126del;g.111G&amp;gt;A mutations induce splicing defects and affect the homeostasis and function of the Integrator complex.<\/jats:p>","DOI":"10.1093\/nar\/gkac1182","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T08:52:46Z","timestamp":1671526366000},"page":"712-727","source":"Crossref","is-referenced-by-count":14,"title":["Mutations in the non-coding<i>RNU4ATAC<\/i>gene affect the homeostasis and function of the Integrator complex"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8834-3096","authenticated-orcid":false,"given":"Fatimat","family":"Almentina\u00a0Ramos\u00a0Shidi","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier, University of Montpellier , CNRS UMR5535, 34293\u00a0 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3623-8750","authenticated-orcid":false,"given":"Audric","family":"Cologne","sequence":"additional","affiliation":[{"name":"INRIA Erable, CNRS LBBE UMR 5558, University Lyon 1, University of Lyon , 69622\u00a0 Villeurbanne , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2666-4457","authenticated-orcid":false,"given":"Marion","family":"Delous","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS , Centre de Recherche en Neurosciences de Lyon U1028 UMR5292, GENDEV, 69500\u00a0 Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2812-5927","authenticated-orcid":false,"given":"Alicia","family":"Besson","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS , Centre de Recherche en Neurosciences de Lyon U1028 UMR5292, GENDEV, 69500\u00a0 Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5496-4604","authenticated-orcid":false,"given":"Audrey","family":"Putoux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS , Centre de Recherche en Neurosciences de Lyon U1028 UMR5292, GENDEV, 69500\u00a0 Bron , France"},{"name":"Clinical Genetics Unit, Department of Genetics , Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Polymalformatifs, Hospices Civils de Lyon, University Lyon 1, Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1302-4357","authenticated-orcid":false,"given":"Anne-Louise","family":"Leutenegger","sequence":"additional","affiliation":[{"name":"Inserm, Universit\u00e9 Paris Cit\u00e9 , NeuroDiderot, UMR1141, 75019\u00a0 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4235-8524","authenticated-orcid":false,"given":"Vincent","family":"Lacroix","sequence":"additional","affiliation":[{"name":"INRIA Erable, CNRS LBBE UMR 5558, University Lyon 1, University of Lyon , 69622\u00a0 Villeurbanne , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-5832","authenticated-orcid":false,"given":"Patrick","family":"Edery","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS , Centre de Recherche en Neurosciences de Lyon U1028 UMR5292, GENDEV, 69500\u00a0 Bron , France"},{"name":"Clinical Genetics Unit, Department of Genetics , Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Polymalformatifs, Hospices Civils de Lyon, University Lyon 1, Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-0160","authenticated-orcid":false,"given":"Sylvie","family":"Mazoyer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS , Centre de Recherche en Neurosciences de Lyon U1028 UMR5292, GENDEV, 69500\u00a0 Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-5802","authenticated-orcid":false,"given":"R\u00e9my","family":"Bordonn\u00e9","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier, University of Montpellier , CNRS UMR5535, 34293\u00a0 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"2023012711491801600_B1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1515\/BC.2005.084","article-title":"Splicing of a rare class of introns by the U12-dependent spliceosome","volume":"386","author":"Will","year":"2005","journal-title":"Biol. Chem."},{"key":"2023012711491801600_B2","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.cell.2009.02.009","article-title":"The spliceosome: design principles of a dynamic RNP machine","volume":"136","author":"Wahl","year":"2009","journal-title":"Cell"},{"key":"2023012711491801600_B3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.tig.2012.01.001","article-title":"New connections between splicing and human disease","volume":"28","author":"Padgett","year":"2012","journal-title":"Trends Genet."},{"key":"2023012711491801600_B4","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/wrna.1141","article-title":"The significant other: splicing by the minor spliceosome","volume":"4","author":"Turunen","year":"2013","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"2023012711491801600_B5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.semcdb.2017.09.036","article-title":"Minor spliceosome and disease","volume":"79","author":"Verma","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"2023012711491801600_B6","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/S0955-0674(00)00211-8","article-title":"Spliceosomal UsnRNP biogenesis, structure and function","volume":"13","author":"Will","year":"2001","journal-title":"Curr. Opin. Cell Biol."},{"key":"2023012711491801600_B7","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1128\/MCB.22.10.3219-3229.2002","article-title":"Human U4\/U6.U5 and U4atac\/U6atac.U5 tri-snRNPs exhibit similar protein compositions","volume":"22","author":"Schneider","year":"2002","journal-title":"Mol. Cell Biol."},{"key":"2023012711491801600_B8","doi-asserted-by":"crossref","first-page":"8885","DOI":"10.1073\/pnas.85.23.8885","article-title":"Additional low-abundance human small nuclear ribonucleoproteins: U11, U12, etc","volume":"85","author":"Montzka","year":"1988","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012711491801600_B9","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1126\/science.273.5283.1824","article-title":"Highly diverged U4 and U6 small nuclear RNAs required for splicing rare AT-AC introns","volume":"273","author":"Tarn","year":"1996","journal-title":"Science"},{"key":"2023012711491801600_B10","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00412-017-0637-6","article-title":"UsnRNP biogenesis: mechanisms and regulation","volume":"126","author":"Gruss","year":"2017","journal-title":"Chromosoma"},{"key":"2023012711491801600_B11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cell.2005.08.019","article-title":"Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II","volume":"123","author":"Baillat","year":"2005","journal-title":"Cell"},{"key":"2023012711491801600_B12","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1042\/BST0381082","article-title":"snRNA 3\u2032 end formation: the dawn of the Integrator complex","volume":"38","author":"Chen","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"2023012711491801600_B13","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/j.1460-2075.1985.tb03857.x","article-title":"Formation of the 3\u2032 end of U1 snRNA is directed by a conserved sequence located downstream of the coding region","volume":"4","author":"Hernandez","year":"1985","journal-title":"EMBO J."},{"key":"2023012711491801600_B14","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S0092-8674(00)80368-2","article-title":"The SMN\u2013SIP1 complex has an essential role in spliceosomal snRNP biogenesis","volume":"90","author":"Fischer","year":"1997","journal-title":"Cell"},{"key":"2023012711491801600_B15","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S0092-8674(00)80367-0","article-title":"The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins","volume":"90","author":"Liu","year":"1997","journal-title":"Cell"},{"key":"2023012711491801600_B16","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1016\/S0960-9822(01)00592-9","article-title":"Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln","volume":"11","author":"Meister","year":"2001","journal-title":"Curr. Biol."},{"key":"2023012711491801600_B17","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1126\/science.1074962","article-title":"Essential role for the SMN complex in the specificity of snRNP assembly","volume":"298","author":"Pellizzoni","year":"2002","journal-title":"Science"},{"key":"2023012711491801600_B18","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(86)90072-3","article-title":"Cap trimethylation of U snRNA is cytoplasmic and dependent on U snRNP protein binding","volume":"46","author":"Mattaj","year":"1986","journal-title":"Cell"},{"key":"2023012711491801600_B19","first-page":"4160","article-title":"m3G cap hypermethylation of U1 small nuclear ribonucleoprotein (snRNP) in vitro: evidence that the U1 small nuclear RNA-(guanosine-N2)-methyltransferase is a non-snRNP cytoplasmic protein that requires a binding site on the Sm core domain","volume":"14","author":"Plessel","year":"1994","journal-title":"Mol. Cell Biol."},{"key":"2023012711491801600_B20","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S1097-2765(02)00484-7","article-title":"Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs requires a conserved methyltransferase that is localized to the nucleolus","volume":"9","author":"Mouaikel","year":"2002","journal-title":"Mol. Cell"},{"key":"2023012711491801600_B21","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1101\/gad.336891.120","article-title":"Competition between maturation and degradation drives human snRNA 3\u2019 end quality control","volume":"34","author":"Lardelli","year":"2020","journal-title":"Genes Dev."},{"key":"2023012711491801600_B22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/ng.3762","article-title":"Biallelic mutations in the 3\u2032 exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing","volume":"49","author":"Lardelli","year":"2017","journal-title":"Nat. Genet."},{"key":"2023012711491801600_B23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1126\/science.1202205","article-title":"Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA","volume":"332","author":"Edery","year":"2011","journal-title":"Science"},{"key":"2023012711491801600_B24","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1126\/science.1200587","article-title":"Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I","volume":"332","author":"He","year":"2011","journal-title":"Science"},{"key":"2023012711491801600_B25","doi-asserted-by":"crossref","first-page":"e0235655","DOI":"10.1371\/journal.pone.0235655","article-title":"Clinical interpretation of variants identified in RNU4ATAC, a non-coding spliceosomal gene","volume":"15","author":"Benoit-Pilven","year":"2020","journal-title":"PLoS One"},{"key":"2023012711491801600_B26","doi-asserted-by":"crossref","first-page":"8718","DOI":"10.1038\/ncomms9718","article-title":"Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing","volume":"6","author":"Merico","year":"2015","journal-title":"Nat. Commun."},{"key":"2023012711491801600_B27","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/ajmg.a.38581","article-title":"The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome","volume":"176","author":"Farach","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"2023012711491801600_B28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41525-017-0024-5","article-title":"A homozygous mutation in the stem II domain of RNU4ATAC causes typical Roifman syndrome","volume":"2","author":"Schejter","year":"2017","journal-title":"NPJ Genom. Med."},{"key":"2023012711491801600_B29","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00439-018-1950-8","article-title":"Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype","volume":"137","author":"Shelihan","year":"2018","journal-title":"Hum. Genet."},{"key":"2023012711491801600_B30","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1261\/rna.045187.114","article-title":"Biochemical defects in minor spliceosome function in the developmental disorder MOPD I","volume":"20","author":"Jafarifar","year":"2014","journal-title":"RNA"},{"key":"2023012711491801600_B31","doi-asserted-by":"crossref","first-page":"D110","DOI":"10.1093\/nar\/gkl796","article-title":"U12DB: a database of orthologous U12-type spliceosomal introns","volume":"35","author":"Alioto","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2023012711491801600_B32","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023012711491801600_B33","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2023012711491801600_B34","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13059-017-1184-4","article-title":"IRFinder: assessing the impact of intron retention on mammalian gene expression","volume":"18","author":"Middleton","year":"2017","journal-title":"Genome Biol."},{"key":"2023012711491801600_B35","article-title":"kissDE: retrieves condition-specific variants in RNA-Seq data","author":"Benoit-Pilven","year":"2021"},{"key":"2023012711491801600_B36","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.1128\/MCB.19.10.6554","article-title":"Spliceosomal U snRNP core assembly: Sm proteins assemble onto an Sm site RNA nonanucleotide in a specific and thermodynamically stable manner","volume":"19","author":"Raker","year":"1999","journal-title":"Mol. Cell Biol."},{"key":"2023012711491801600_B37","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nsmb.1415","article-title":"Phosphorylation of human PRP28 by SRPK2 is required for integration of the U4\/U6-U5 tri-snRNP into the spliceosome","volume":"15","author":"Mathew","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2023012711491801600_B38","doi-asserted-by":"crossref","first-page":"6756","DOI":"10.1128\/MCB.18.11.6756","article-title":"The human U5-220kD protein (hPrp8) forms a stable RNA-free complex with several U5-specific proteins, including an RNA unwindase, a homologue of ribosomal elongation factor EF-2, and a novel WD-40 protein","volume":"18","author":"Achsel","year":"1998","journal-title":"Mol. Cell Biol."},{"key":"2023012711491801600_B39","doi-asserted-by":"crossref","first-page":"pdb.prot3865","DOI":"10.1101\/pdb.prot3865","article-title":"Rapid amplification of 3\u2019 cDNA ends (3\u2019-RACE)","volume":"2006","author":"Sambrook","year":"2006","journal-title":"Cold Spring Harb. Protoc."},{"key":"2023012711491801600_B40","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.1038\/s41598-018-21770-7","article-title":"Complementarity of assembly-first and mapping-first approaches for alternative splicing annotation and differential analysis from RNAseq data","volume":"8","author":"Benoit-Pilven","year":"2018","journal-title":"Sci. Rep."},{"key":"2023012711491801600_B41","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1261\/rna.071423.119","article-title":"New insights into minor splicing\u2014a transcriptomic analysis of cells derived from TALS patients","volume":"25","author":"Cologne","year":"2019","journal-title":"RNA"},{"key":"2023012711491801600_B42","first-page":"1","article-title":"Gene set enrichment analysis with topGO","volume":"27","author":"Alexa","year":"2009","journal-title":"Bioconductor Improv."},{"key":"2023012711491801600_B43","doi-asserted-by":"crossref","DOI":"10.1101\/2021.12.12.21266616","article-title":"Deficiency of the minor spliceosome component U4atac snRNA secondarily results in ciliary defects","author":"Khatri","year":"2021"},{"key":"2023012711491801600_B44","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/wrna.1174","article-title":"Non-mRNA 3\u2032 end formation: how the other half lives","volume":"4","author":"Peart","year":"2013","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"2023012711491801600_B45","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1073\/pnas.1616605114","article-title":"Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance","volume":"114","author":"Wu","year":"2017","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012711491801600_B46","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.tibs.2020.07.004","article-title":"The integrator complex in transcription and development","volume":"45","author":"Mendoza-Figueroa","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"2023012711491801600_B47","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1038\/s41467-020-17232-2","article-title":"INTS10\u2013INTS13\u2013INTS14 form a functional module of Integrator that binds nucleic acids and the cleavage module","volume":"11","author":"Sabath","year":"2020","journal-title":"Nat. Commun."},{"key":"2023012711491801600_B48","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/21541264.2022.2047583","article-title":"Emerging insights into the function and structure of the Integrator complex","volume":"12","author":"Pfleiderer","year":"2021","journal-title":"Transcription"},{"key":"2023012711491801600_B49","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/0022-2836(82)90392-8","article-title":"Structural organization of ribonucleoproteins containing small nuclear RNAs from HeLa cells. Proteins interact closely with a similar structural domain of U1, U2, U4 and U5 small nuclear rnas","volume":"162","author":"Liautard","year":"1982","journal-title":"J. Mol. Biol."},{"key":"2023012711491801600_B50","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev.ge.22.120188.002131","article-title":"Spliceosomal snRNAs","volume":"22","author":"Guthrie","year":"1988","journal-title":"Annu. Rev. Genet."},{"key":"2023012711491801600_B51","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.1093\/nar\/27.20.3986","article-title":"Cloning and mutational analysis of the Leptomonas seymouri U5 snRNA gene: function of the Sm site in core RNP formation and nuclear localization","volume":"27","author":"Bell","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"2023012711491801600_B52","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1073\/pnas.90.3.848","article-title":"Convergent transcripts of the yeast PRP38-SMD1 locus encode two essential splicing factors, including the D1 core polypeptide of small nuclear ribonucleoprotein particles","volume":"90","author":"Rymond","year":"1993","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012711491801600_B53","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0378-1119(96)00230-2","article-title":"The yeast SME1 gene encodes the homologue of the human E core protein","volume":"176","author":"Bordonn\u00e9","year":"1996","journal-title":"Gene"},{"key":"2023012711491801600_B54","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1093\/nar\/gkab048","article-title":"The integrity of the U12 snRNA 3\u2019 stem\u2013loop is necessary for its overall stability","volume":"49","author":"Norppa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2023012711491801600_B55","doi-asserted-by":"crossref","first-page":"20564","DOI":"10.1074\/jbc.M110.132530","article-title":"The integrator complex recognizes a new double mark on the RNA polymerase II carboxyl-terminal domain","volume":"285","author":"Egloff","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2023012711491801600_B56","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.tibs.2015.03.005","article-title":"Integrator: surprisingly diverse functions in gene expression","volume":"40","author":"Baillat","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"2023012711491801600_B57","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1093\/nar\/gky100","article-title":"Integrator subunit 4 is a \u2018Symplekin-like\u2019 scaffold that associates with INTS9\/11 to form the Integrator cleavage module","volume":"46","author":"Albrecht","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2023012711491801600_B58","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1038\/ncomms5263","article-title":"DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes","volume":"5","author":"Yamamoto","year":"2014","journal-title":"Nat. Commun."},{"key":"2023012711491801600_B59","doi-asserted-by":"crossref","first-page":"e1006809","DOI":"10.1371\/journal.pgen.1006809","article-title":"Human mutations in integrator complex subunits link transcriptome integrity to brain development","volume":"13","author":"Oegema","year":"2017","journal-title":"PLoS Genet"},{"key":"2023012711491801600_B60","doi-asserted-by":"crossref","first-page":"170073","DOI":"10.1098\/rsob.170073","article-title":"Regulation of expression of human RNA polymerase II-transcribed snRNA genes","volume":"7","author":"Guiro","year":"2017","journal-title":"Open Biol"},{"key":"2023012711491801600_B61","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1128\/MCB.00943-10","article-title":"A subset of Drosophila integrator proteins is essential for efficient U7 snRNA and spliceosomal snRNA 3\u2019-end formation","volume":"31","author":"Ezzeddine","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"2023012711491801600_B62","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1093\/emboj\/cdg430","article-title":"The 3\u2019 ends of human pre-snRNAs are produced by RNA polymerase II CTD-dependent RNA processing","volume":"22","author":"Uguen","year":"2003","journal-title":"EMBO J"},{"key":"2023012711491801600_B63","doi-asserted-by":"crossref","first-page":"e1007981","DOI":"10.1371\/journal.pgen.1007981","article-title":"Disruption of the Caenorhabditis elegans Integrator complex triggers a non-conventional transcriptional mechanism beyond snRNA genes","volume":"15","author":"G\u00f3mez-Orte","year":"2019","journal-title":"PLoS Genet."},{"key":"2023012711491801600_B64","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.molcel.2020.12.002","article-title":"Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression","volume":"81","author":"Rosa-Mercado","year":"2021","journal-title":"Mol. Cell"},{"key":"2023012711491801600_B65","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0092-8674(87)90614-3","article-title":"Interactions between small nuclear ribonucleoprotein particles in formation of spliceosomes","volume":"49","author":"Konarska","year":"1987","journal-title":"Cell"},{"key":"2023012711491801600_B66","first-page":"3350","article-title":"U5 small nuclear ribonucleoprotein: RNA structure analysis and ATP-dependent interaction with U4\/U6","volume":"9","author":"Black","year":"1989","journal-title":"Mol. Cell Biol."},{"key":"2023012711491801600_B67","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/hmg\/ddq508","article-title":"Impaired minor tri-snRNP assembly generates differential splicing defects of U12-type introns in lymphoblasts derived from a type I SMA patient","volume":"20","author":"Boulisfane","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2023012711491801600_B68","doi-asserted-by":"crossref","first-page":"e106536","DOI":"10.15252\/embj.2020106536","article-title":"Chromosomal instability by mutations in the novel minor spliceosome component CENATAC","volume":"40","author":"de\u00a0Wolf","year":"2021","journal-title":"EMBO J"},{"key":"2023012711491801600_B69","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1101\/gad.4.7.1185","article-title":"Domains of yeast U4 spliceosomal RNA required for PRP4 protein binding, snRNP\u2013snRNP interactions, and pre-mRNA splicing in vivo","volume":"4","author":"Bordonn\u00e9","year":"1990","journal-title":"Genes Dev"},{"key":"2023012711491801600_B70","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1093\/nar\/gkf609","article-title":"Domains of human U4atac snRNA required for U12-dependent splicing in vivo","volume":"30","author":"Shukla","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012711491801600_B71","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1002\/j.1460-2075.1990.tb07541.x","article-title":"Domains of U4 and U6 snRNAs required for snRNP assembly and splicing complementation in Xenopus oocytes","volume":"9","author":"Vankan","year":"1990","journal-title":"EMBO J."},{"key":"2023012711491801600_B72","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/j.1460-2075.1992.tb05056.x","article-title":"Roles of U4 and U6 snRNAs in the assembly of splicing complexes","volume":"11","author":"Vankan","year":"1992","journal-title":"EMBO J."},{"key":"2023012711491801600_B73","doi-asserted-by":"crossref","first-page":"6223","DOI":"10.1093\/nar\/18.21.6223","article-title":"Conserved domains of human U4 snRNA required for snRNP and spliceosome assembly","volume":"18","author":"Wersig","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"2023012711491801600_B74","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0014-4827(92)90447-G","article-title":"Assembly and nuclear transport of the U4 and U4\/U6 snRNPs","volume":"199","author":"Wersig","year":"1992","journal-title":"Exp. Cell Res."},{"key":"2023012711491801600_B75","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1128\/MCB.15.3.1274","article-title":"Mutational analysis of Saccharomyces cerevisiae U4 small nuclear RNA identifies functionally important domains","volume":"15","author":"Hu","year":"1995","journal-title":"Mol. Cell Biol."},{"key":"2023012711491801600_B76","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1261\/rna.031757.111","article-title":"In vitro reconstitution of yeast splicing with U4 snRNA reveals multiple roles for the 3\u2019 stem\u2013loop","volume":"18","author":"Hayduk","year":"2012","journal-title":"RNA"},{"key":"2023012711491801600_B77","doi-asserted-by":"crossref","first-page":"eabg0879","DOI":"10.1126\/science.abg0879","article-title":"Structure of the activated human minor spliceosome","volume":"371","author":"Bai","year":"2021","journal-title":"Science"},{"key":"2023012711491801600_B78","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.cell.2017.07.011","article-title":"Cryo-EM structure of a pre-catalytic human spliceosome primed for activation","volume":"170","author":"Bertram","year":"2017","journal-title":"Cell"},{"key":"2023012711491801600_B79","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/s41422-018-0094-7","article-title":"Structures of the human pre-catalytic spliceosome and its precursor spliceosome","volume":"28","author":"Zhan","year":"2018","journal-title":"Cell Res."},{"key":"2023012711491801600_B80","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41586-018-0323-8","article-title":"Prespliceosome structure provides insights into spliceosome assembly and regulation","volume":"559","author":"Plaschka","year":"2018","journal-title":"Nature"},{"key":"2023012711491801600_B81","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.jaci.2017.11.061","article-title":"Abnormal differentiation of B cells and megakaryocytes in patients with Roifman syndrome","volume":"142","author":"Heremans","year":"2018","journal-title":"J. Allergy Clin. Immunol"},{"key":"2023012711491801600_B82","doi-asserted-by":"crossref","first-page":"3524","DOI":"10.1093\/nar\/gkab118","article-title":"Disruption of exon-bridging interactions between the minor and major spliceosomes results in alternative splicing around minor introns","volume":"49","author":"Olthof","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2023012711491801600_B83","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.molcel.2020.12.014","article-title":"Integrator is a genome-wide attenuator of non-productive transcription","volume":"81","author":"Lykke-Andersen","year":"2021","journal-title":"Mol. Cell"},{"key":"2023012711491801600_B84","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.molcel.2014.08.004","article-title":"Integrator regulates transcriptional initiation and pause release following activation","volume":"56","author":"Gardini","year":"2014","journal-title":"Mol. Cell"},{"key":"2023012711491801600_B85","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/cr.2015.19","article-title":"The Integrator complex controls the termination of transcription at diverse classes of gene targets","volume":"25","author":"Skaar","year":"2015","journal-title":"Cell Res."},{"key":"2023012711491801600_B86","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nature14906","article-title":"Integrator mediates the biogenesis of enhancer RNAs","volume":"525","author":"Lai","year":"2015","journal-title":"Nature"},{"key":"2023012711491801600_B87","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.molcel.2018.10.011","article-title":"Deregulated expression of mammalian lncRNA through loss of SPT6 induces R-loop formation, replication stress, and cellular senescence","volume":"72","author":"Nojima","year":"2018","journal-title":"Mol. Cell"},{"key":"2023012711491801600_B88","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.molcel.2019.10.034","article-title":"The integrator complex attenuates promoter-proximal transcription at protein-coding genes","volume":"76","author":"Elrod","year":"2019","journal-title":"Mol. Cell"},{"key":"2023012711491801600_B89","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1101\/gad.330167.119","article-title":"The Integrator complex cleaves nascent mRNAs to attenuate transcription","volume":"33","author":"Tatomer","year":"2019","journal-title":"Genes Dev."},{"key":"2023012711491801600_B90","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1038\/ncomms6531","article-title":"Integrator complex regulates NELF-mediated RNA polymerase II pause\/release and processivity at coding genes","volume":"5","author":"Stadelmayer","year":"2014","journal-title":"Nat. Commun."},{"key":"2023012711491801600_B91","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1017\/S1355838202017156","article-title":"A revised model for U4atac\/U6atac snRNA base pairing","volume":"8","author":"Padgett","year":"2002","journal-title":"RNA"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/51\/2\/712\/48929550\/gkac1182.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/51\/2\/712\/48929550\/gkac1182.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T02:04:01Z","timestamp":1701482641000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/51\/2\/712\/6946993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":91,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,12,20]]},"published-print":{"date-parts":[[2023,1,25]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkac1182","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,25]]},"published":{"date-parts":[[2022,12,20]]}}}