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Sde2 is an intron‐specific pre‐ mRNA splicing regulator activated by ubiquitin‐like processing
Author(s) -
Thakran Poonam,
Pandit Prashant Arun,
Datta Sumanjit,
Kolathur Kiran Kumar,
Pleiss Jeffrey A,
Mishra Shravan Kumar
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201796751
Subject(s) - biology , intron , rna splicing , regulator , messenger rna , microbiology and biotechnology , precursor mrna , ubiquitin , genetics , rna , gene
The expression of intron‐containing genes in eukaryotes requires generation of protein‐coding messenger RNA s ( mRNA s) via RNA splicing, whereby the spliceosome removes non‐coding introns from pre‐ mRNA s 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‐ mRNA s 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‐ mRNA s. 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‐ mRNA s in fission yeast.