{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:09:11Z","timestamp":1791947351389,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,2,9]],"date-time":"2015-02-09T00:00:00Z","timestamp":1423440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In eukaryotes, pre-mRNA splicing is an essential step for gene expression.  We have been analyzing post-splicing intron turnover steps in higher eukaryotes. Here,  we report protein interaction between human Debranching enzyme 1 (hDbr1) and several factors found in the Intron Large (IL) complex, which is an intermediate complex of the intron degradation pathway. The hDbr1 protein specifically interacts with xeroderma pigmentosum, complementeation group A (XPA)-binding protein 2 (Xab2). We also attempted to identify specific interactors of hDbr1. Co-immunoprecipitation experiments followed by mass spectrometry analysis identified a novel protein as one of the specific interactors of hDbr1. This protein is well conserved among many species and shows the highest similarity to yeast Drn1, so it is designated as human Dbr1 associated ribonuclease 1 (hDrn1). hDrn1 directly interacts with hDbr1 through protein\u2013protein interaction. Furthermore, hDrn1 shuttles between the nucleus and the cytoplasm, as hDbr1 protein does. These findings suggest that hDrn1 has roles in both the nucleus and the cytoplasm, which are highly likely to involve hDbr1.<\/jats:p>","DOI":"10.3390\/ijms16023705","type":"journal-article","created":{"date-parts":[[2015,2,9]],"date-time":"2015-02-09T10:17:04Z","timestamp":1423477024000},"page":"3705-3721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Identification of the Specific Interactors of the Human Lariat RNA Debranching Enzyme 1 Protein"],"prefix":"10.3390","volume":"16","author":[{"given":"So","family":"Masaki","sequence":"first","affiliation":[{"name":"Medical Innovation Center, Laboratory for Malignancy Control Research,  Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan"},{"name":"Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan"},{"name":"Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science,  Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kaida","sequence":"additional","affiliation":[{"name":"Frontier Research Core for Life Sciences, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Hata","sequence":"additional","affiliation":[{"name":"Medical Innovation Center, Laboratory for Malignancy Control Research,  Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Satoh","sequence":"additional","affiliation":[{"name":"Frontier Research Core for Life Sciences, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsuhito","family":"Ohno","sequence":"additional","affiliation":[{"name":"Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Medical Innovation Center, Laboratory for Malignancy Control Research,  Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan"},{"name":"Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan"},{"name":"Medical Top Track Program, Medical Research Institute, Tokyo Dental and Medical University, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"International Human Genome Sequencing Consortium (2004). Finishing the euchromatic sequence of the human genome. Nature, 431, 931\u2013945.","DOI":"10.1038\/nature03001"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"International Human Genome Sequencing Consortium (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860\u2013921.","DOI":"10.1038\/35057062"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrm760","article-title":"Messenger-RNA-binding proteins and the messages they carry","volume":"3","author":"Dreyfuss","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0955-0674(00)00212-X","article-title":"Pre-mRNA splicing in the new millennium","volume":"13","author":"Hastings","year":"2001","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/416499a","article-title":"An extensive network of coupling among gene expression machines","volume":"416","author":"Maniatis","year":"2002","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S1097-2765(03)00270-3","article-title":"Pre-mRNA splicing: Awash in a sea of proteins","volume":"12","author":"Jurica","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.molcel.2006.07.011","article-title":"A spliceosomal intron binding protein, IBP160, links position-dependent assembly of intron-encoded box C\/D snoRNP to pre-mRNA splicing","volume":"23","author":"Hirose","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S1097-2765(03)00267-3","article-title":"Splicing-dependent and -independent modes of assembly for intron-encoded box C\/D snoRNPs in mammalian cells","volume":"12","author":"Hirose","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12914","DOI":"10.1073\/pnas.231490998","article-title":"Position within the host intron is critical for efficient processing of box C\/D snoRNAs in mammalian cells","volume":"98","author":"Hirose","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1128\/MCB.00360-09","article-title":"Functional association of the microprocessor complex with the spliceosome","volume":"29","author":"Kataoka","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/sj.emboj.7601512","article-title":"Processing of intronic microRNAs","volume":"26","author":"Kim","year":"2007","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.tcb.2009.10.004","article-title":"Nuclear networking fashions pre-messenger RNA and primary microRNA transcripts for function","volume":"20","author":"Pawlicki","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0092-8674(02)00645-1","article-title":"Nuclear RNA turnover","volume":"108","author":"Moore","year":"2002","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1093\/nar\/28.18.3666","article-title":"Human RNA lariat debranching enzyme cDNA complements the phenotypes of Saccharomyces cerevisiae Dbr1 and Schizosaccharomyces pombe dbr1 mutants","volume":"28","author":"Kim","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1128\/MCB.17.2.809","article-title":"Severe growth defect in a Schizosaccharomyces pombe mutant defective in intron lariat degradation","volume":"17","author":"Nam","year":"1997","journal-title":"Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/srep01090","article-title":"hDbr1 is a nucleocytoplasmic shuttling protein with a protein phosphatase-like motif essential for debranching activity","volume":"3","author":"Kataoka","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/nar\/gkn1002","article-title":"Isolation and characterization of post-splicing lariat-intron complexes","volume":"37","author":"Yoshimoto","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/gtc.12114","article-title":"Identification of a novel component C2ORF3 in the lariat-intron complex: Lack of C2ORF3 interferes with pre-mRNA splicing via intron turnover pathway","volume":"19","author":"Yoshimoto","year":"2014","journal-title":"Genes Cells"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1261\/rna.044602.114","article-title":"A homolog of lariat-debranching enzyme modulates turnover of branched RNA","volume":"20","author":"Garrey","year":"2014","journal-title":"RNA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.cell.2005.08.029","article-title":"A human protein-protein interaction network: A resource for annotating the proteome","volume":"122","author":"Stelzl","year":"2005","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nature13695","article-title":"Saturation editing of genomic regions by multiplex homology-directed repair","volume":"513","author":"Findlay","year":"2014","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1074\/jbc.M309106200","article-title":"An Arabidopsis RNA lariat debranching enzyme is essential for embryogenesis","volume":"279","author":"Wang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.dnarep.2004.12.004","article-title":"Disruption of mouse Xab2 gene involved in pre-mRNA splicing, transcription and transcription-coupled DNA repair results in preimplantation lethality","volume":"4","author":"Yonemasu","year":"2005","journal-title":"DNA Repair (Amst)"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1101\/gad.202184.112","article-title":"Stable intronic sequence RNA (sisRNA), a new class of noncoding RNA from the oocyte nucleus of Xenopus tropicalis","volume":"26","author":"Gardner","year":"2012","journal-title":"Genes Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1261\/rna.045781.114","article-title":"Lariat intronic RNAs in the cytoplasm of Xenopus tropicalis oocytes","volume":"20","author":"Talhouarne","year":"2014","journal-title":"RNA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16919","DOI":"10.1074\/jbc.M005104200","article-title":"Localization and stability of introns spliced from the Pem homeobox gene","volume":"276","author":"Clement","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S1097-2765(03)00488-X","article-title":"Cytoplasmic degradation of splice-defective pre-mRNAs and intermediates","volume":"12","author":"Hilleren","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molcel.2014.08.019","article-title":"CircRNA biogenesis competes with pre-mRNA splicing","volume":"56","author":"Meyer","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature11993","article-title":"Natural RNA circles function as efficient microRNA sponges","volume":"495","author":"Hansen","year":"2013","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.celrep.2014.12.019","article-title":"Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals","volume":"10","author":"Ivanov","year":"2015","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature11928","article-title":"Circular RNAs are a large class of animal RNAs with regulatory potency","volume":"495","author":"Memczak","year":"2013","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.celrep.2014.12.002","article-title":"Exon circularization requires canonical splice signals","volume":"10","author":"Starke","year":"2015","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S1097-2765(00)00065-4","article-title":"Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm","volume":"6","author":"Kataoka","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1126\/science.1062829","article-title":"Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex","volume":"293","author":"Kim","year":"2001","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1093\/emboj\/20.22.6424","article-title":"Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon\u2013exon junction complex","volume":"20","author":"Kataoka","year":"2001","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/srep00092","article-title":"Specific Y14 domains mediate its nucleo-cytoplasmic shuttling and association with spliced mRNA","volume":"1","author":"Kataoka","year":"2011","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7009","DOI":"10.1074\/jbc.M307692200","article-title":"A simple whole cell lysate system for in vitro splicing reveals a stepwise assembly of the exon-exon junction complex","volume":"279","author":"Kataoka","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1083\/jcb.138.6.1181","article-title":"Transportin-mediated nuclear import of heterogeneous nuclear RNP proteins","volume":"138","author":"Siomi","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0092-8674(95)90119-1","article-title":"A nuclear export signal in hnRNP A1: A signal-mediated, temperature-dependent nuclear protein export pathway","volume":"83","author":"Michael","year":"1995","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1083\/jcb.134.6.1365","article-title":"The hnRNP C proteins contain a nuclear retention sequence that can override nuclear export signals","volume":"134","author":"Nakielny","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/355730a0","article-title":"Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm","volume":"355","author":"Dreyfuss","year":"1992","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/2\/3705\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:42:28Z","timestamp":1760215348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/2\/3705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,9]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,2]]}},"alternative-id":["ijms16023705"],"URL":"https:\/\/doi.org\/10.3390\/ijms16023705","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,9]]}}}