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EMBO J. 2018 Jan 4;37(1):89-101. doi: 10.15252/embj.201796751. Epub 2017 Sep 25.

Sde2 is an intron-specific pre-mRNA splicing regulator activated by ubiquitin-like processing.

Author information

1
Max Planck - DST Partner Group, Department of Biological Sciences, Centre for Protein Science Design and Engineering, Indian Institute of Science Education and Research (IISER) Mohali, Mohali, Punjab, India.
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
3
Max Planck - DST Partner Group, Department of Biological Sciences, Centre for Protein Science Design and Engineering, Indian Institute of Science Education and Research (IISER) Mohali, Mohali, Punjab, India skmishra@iisermohali.ac.in mishra.iiserm@gmail.com.

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.

KEYWORDS:

N‐end rule pathway; deubiquitinating enzymes; intron‐specific pre‐mRNA splicing; telomeric silencing; ubiquitin‐like processing

PMID:
28947618
PMCID:
PMC5753039
[Available on 2019-01-04]
DOI:
10.15252/embj.201796751

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