RRC ID |
54360
|
著者 |
Thakran P, Pandit PA, Datta S, Kolathur KK, Pleiss JA, Mishra SK.
|
タイトル |
Sde2 is an intron-specific pre-mRNA splicing regulator activated by ubiquitin-like processing.
|
ジャーナル |
EMBO J
|
Abstract |
The expression of intron-containing genes in eukaryotes requires generation of protein-coding messenger RNAs (mRNAs) via RNA splicing, whereby the spliceosome removes non-coding introns from pre-mRNAs and joins exons. Spliceosomes must ensure accurate removal of highly diverse introns. We show that Sde2 is a ubiquitin-fold-containing splicing regulator that supports splicing of selected pre-mRNAs in an intron-specific manner in Schizosaccharomyces pombe Both fission yeast and human Sde2 are translated as inactive precursor proteins harbouring the ubiquitin-fold domain linked through an invariant GGKGG motif to a C-terminal domain (referred to as Sde2-C). Precursor processing after the first di-glycine motif by the ubiquitin-specific proteases Ubp5 and Ubp15 generates a short-lived activated Sde2-C fragment with an N-terminal lysine residue, which subsequently gets incorporated into spliceosomes. Absence of Sde2 or defects in Sde2 activation both result in inefficient excision of selected introns from a subset of pre-mRNAs. Sde2 facilitates spliceosomal association of Cactin/Cay1, with a functional link between Sde2 and Cactin further supported by genetic interactions and pre-mRNA splicing assays. These findings suggest that ubiquitin-like processing of Sde2 into a short-lived activated form may function as a checkpoint to ensure proper splicing of certain pre-mRNAs in fission yeast.
|
巻・号 |
37(1)
|
ページ |
89-101
|
公開日 |
2018-1-4
|
DOI |
10.15252/embj.201796751
|
PII |
embj.201796751
|
PMID |
28947618
|
PMC |
PMC5753039
|
MeSH |
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Genomic Instability
Humans
Introns*
RNA Precursors / genetics
RNA Splicing*
RNA, Fungal / genetics
RNA, Fungal / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Schizosaccharomyces / genetics*
Schizosaccharomyces / metabolism
Schizosaccharomyces pombe Proteins / genetics
Schizosaccharomyces pombe Proteins / metabolism*
Spliceosomes
Ubiquitin / metabolism*
|
IF |
9.889
|
引用数 |
10
|
リソース情報 |
酵母 |
FY23646
FY23631
FY23639 |