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Ubiquitin-like processing of the conserved splicing regulator Sde2 promotes telomeric silencing and genome stability

ABSTRACT: Intron-containing gene expression in eukaryotes proceeds through the process of RNA splicing to generate protein-coding messenger RNAs (mRNAs). Herein a large and dynamic ribonucleoprotein complex — the spliceosome — removes non-coding introns from pre-mRNAs and joins exons. Spliceosomes must also ensure accurate and timely removal of diverse and highly prevalent introns. Here we show that Sde2 is a conserved splicing regulator, contains a ubiquitin fold, and supports splicing of a subset of pre-mRNAs in an intron-specific manner in Schizosaccharomyces pombe. Its orthologs in S. pombe and humans are synthesized as precursors harboring a ubiquitin fold, followed by an invariant GGKGG motif and an uncharacterized C-terminal domain (referred to as Sde2-C). The precursor must be cleaved at GG^K by the ubiquitin specific proteases Ubp5 and Ubp15 to produce the Sde2-C protein containing a lysine residue at its C-terminus, and is a substrate of the N-end rule pathway of proteasomal degradation. The truncated Sde2-C functions as a component of the spliceosome, and loss of Sde2-C results in inefficient splicing of selected introns from target genes having functions in DNA replication, transcription and telomeric silencing. Thus, the ubiquitin-like processing of Sde2 — associated with its regulation by the N-end rule pathway — contributes to genomic stability in S. pombe through specific pre-mRNA splicing events.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE97097 | GEO | 2017/09/22

SECONDARY ACCESSION(S): PRJNA380667

REPOSITORIES: GEO

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