ISG20 and nuclear exosome promote destabilization of nascent transcripts for spliceosomal U snRNAs and U1 variants. (2nd December 2020)

• Record Type: Journal Article
• Authors: Kawamoto, Takahito; Yoshimoto, Rei; Taniguchi, Ichiro; Kitabatake, Makoto; Ohno, Mutsuhito
• Is Part Of: Genes to cells. Volume 26:Number 1(2021)
• Page Start: 18
• Page End: 30
• Publication Date: 2020-12-02
• Subjects: exosome -- ISG20 -- spliceosomal U snRNAs -- TOE1 -- U1 variants; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12817
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: 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. Abstract : 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