ISG20 and nuclear exosome promote destabilization of nascent transcripts for spliceosomal U snRNAs and U1 variants

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, pontocereb...

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Bibliographic Details
Published in:Genes to cells : devoted to molecular & cellular mechanisms 2021-01, Vol.26 (1), p.18-30
Main Authors: Kawamoto, Takahito, Yoshimoto, Rei, Taniguchi, Ichiro, Kitabatake, Makoto, Ohno, Mutsuhito
Format: Article
Language:English
Subjects:
Exonuclease
exosome
Hypoplasia
Interferon
ISG20
Maturation
Quality control
snRNA
spliceosomal U snRNAs
TOE1
U1 variants
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Summary: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. In the regular situations, 3′‐short extra tail sequence of U snRNA precursors is trimmed by TOE1 to their mature forms. However, aberrant U snRNA products caused by erroneous U snRNA biogenesis as well as regular U1 variants are degraded by Interferon‐stimulated gene 20‐kDa protein (ISG20) and/or the nuclear exosome
ISSN:1356-9597
1365-2443
DOI:10.1111/gtc.12817