{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:59:00Z","timestamp":1782435540492,"version":"3.54.5"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane and Aatos Erkko Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["308657"],"award-info":[{"award-number":["308657"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007797","name":"University of Helsinki","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Disruption of minor spliceosome functions underlies several genetic diseases with mutations in the minor spliceosome-specific small nuclear RNAs (snRNAs) and proteins. Here, we define the molecular outcome of the U12 snRNA mutation (84C&amp;gt;U) resulting in an early-onset form of cerebellar ataxia. To understand the molecular consequences of the U12 snRNA mutation, we created cell lines harboring the 84C&amp;gt;T mutation in the U12 snRNA gene (RNU12). We show that the 84C&amp;gt;U mutation leads to accelerated decay of the snRNA, resulting in significantly reduced steady-state U12 snRNA levels. Additionally, the mutation leads to accumulation of 3\u2032-truncated forms of U12 snRNA, which have undergone the cytoplasmic steps of snRNP biogenesis. Our data suggests that the 84C&amp;gt;U-mutant snRNA is targeted for decay following reimport into the nucleus, and that the U12 snRNA fragments are decay intermediates that result from the stalling of a 3\u2032-to-5\u2032 exonuclease. Finally, we show that several other single-nucleotide variants in the 3\u2032 stem-loop of U12 snRNA that are segregating in the human population are also highly destabilizing. This suggests that the 3\u2032 stem-loop is important for the overall stability of the U12 snRNA and that additional disease-causing mutations are likely to exist in this region.<\/jats:p>","DOI":"10.1093\/nar\/gkab048","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T12:07:33Z","timestamp":1612699653000},"page":"2835-2847","source":"Crossref","is-referenced-by-count":14,"title":["The integrity of the U12 snRNA 3\u2032 stem\u2013loop is necessary for its overall stability"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-3218","authenticated-orcid":false,"given":"Antto J","family":"Norppa","sequence":"first","affiliation":[{"name":"Institute of Biotechnology, P.O. Box 56, Viikinkaari 5, University of Helsinki,\u00a0FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1732-4808","authenticated-orcid":false,"given":"Mikko J","family":"Frilander","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, P.O. Box 56, Viikinkaari 5, University of Helsinki,\u00a0FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"2021031723330710400_B1","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1126\/science.271.5256.1716","article-title":"Requirement of U12 snRNA for in vivo splicing of a minor class of eukaryotic nuclear pre-mRNA introns","volume":"271","author":"Hall","year":"1996","journal-title":"Science"},{"key":"2021031723330710400_B2","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0092-8674(00)81057-0","article-title":"A novel spliceosome containing U11, U12 and U5 snRNPs excises a minor class (AT-AC) intron in vitro","volume":"84","author":"Tarn","year":"1996","journal-title":"Cell"},{"key":"2021031723330710400_B3","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":"2021031723330710400_B4","first-page":"227","article-title":"U11 snRNA interacts in vivo with the 5\u2032 splice site of U12-dependent (AU-AC) pre-mRNA introns","volume":"3","author":"Kolossova","year":"1997","journal-title":"RNA"},{"key":"2021031723330710400_B5","doi-asserted-by":"crossref","first-page":"6030","DOI":"10.1073\/pnas.94.12.6030","article-title":"Site-specific crosslinking of mammalian U11 and U6atac to the 5\u2032 splice site of an AT-AC intron","volume":"94","author":"Yu","year":"1997","journal-title":"Proc. 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