PMID- 33147372 OWN - NLM STAT- MEDLINE DCOM- 20210706 LR - 20210706 IS - 1365-2443 (Electronic) IS - 1356-9597 (Linking) VI - 26 IP - 1 DP - 2021 Jan TI - ISG20 and nuclear exosome promote destabilization of nascent transcripts for spliceosomal U snRNAs and U1 variants. PG - 18-30 LID - 10.1111/gtc.12817 [doi] AB - Primary RNA transcripts are processed in a plethora of ways to become mature functional forms. In one example, human spliceosomal U snRNAs are matured at their 3'-end by an exonuclease termed TOE1. This process is important because mutations in TOE1 gene can cause a human genetic disease, pontocerebellar hypoplasia (PCH). Nevertheless, TOE1 may not be the only maturation exonuclease for U snRNAs in the cell. Here, we biochemically identify two exonucleolytic factors, Interferon-stimulated gene 20-kDa protein (ISG20) and the nuclear exosome as such candidates, using a newly developed in vitro system that recapitulates 3'-end maturation of U1 snRNA. However, extensive 3'-end sequencing of endogenous U1 snRNA of the knockdown (KD) cells revealed that these factors are not the maturation factors per se. Instead, the nascent transcripts of the spliceosomal U snRNAs as well as of unstable U1 variants were found to increase in quantity upon KD of the factors. These results indicated that ISG20 and the nuclear exosome promote the degradation of nascent spliceosomal U snRNAs and U1 variants, and therefore implied their role in the quality control of newly synthesized U snRNAs. CI - (c) 2020 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd. FAU - Kawamoto, Takahito AU - Kawamoto T AUID- ORCID: 0000-0002-0532-9214 AD - Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan. FAU - Yoshimoto, Rei AU - Yoshimoto R AD - Department of Applied Biological Sciences, Faculty of Agriculture, Setsunan University, Hirakata, Japan. FAU - Taniguchi, Ichiro AU - Taniguchi I AD - Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan. FAU - Kitabatake, Makoto AU - Kitabatake M AD - Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan. FAU - Ohno, Mutsuhito AU - Ohno M AD - Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan. LA - eng GR - 25251004/Ministry of Education, Culture, Sports, Science and Technology/ GR - 26113004/Ministry of Education, Culture, Sports, Science and Technology/ PT - Journal Article DEP - 20201202 PL - England TA - Genes Cells JT - Genes to cells : devoted to molecular & cellular mechanisms JID - 9607379 RN - 0 (Nuclear Proteins) RN - 0 (RNA, Small Nuclear) RN - 0 (TOE1 protein, human) RN - 0 (U1 small nuclear RNA) RN - EC 3.1.- (Exoribonucleases) RN - EC 3.1.- (ISG20 protein, human) SB - IM MH - Cell Nucleus/metabolism MH - Exoribonucleases/genetics/*metabolism MH - Exosomes/*metabolism MH - HeLa Cells MH - Humans MH - Nuclear Proteins/genetics/metabolism MH - RNA Stability MH - RNA, Small Nuclear/genetics/*metabolism MH - Spliceosomes/*metabolism OTO - NOTNLM OT - ISG20 OT - TOE1 OT - U1 variants OT - exosome OT - spliceosomal U snRNAs EDAT- 2020/11/05 06:00 MHDA- 2021/07/07 06:00 CRDT- 2020/11/04 17:12 PHST- 2020/10/09 00:00 [received] PHST- 2020/10/29 00:00 [revised] PHST- 2020/10/29 00:00 [accepted] PHST- 2020/11/05 06:00 [pubmed] PHST- 2021/07/07 06:00 [medline] PHST- 2020/11/04 17:12 [entrez] AID - 10.1111/gtc.12817 [doi] PST - ppublish SO - Genes Cells. 2021 Jan;26(1):18-30. doi: 10.1111/gtc.12817. Epub 2020 Dec 2.