Abstract:
:Phosphorylation of the spliceosome is essential for RNA splicing, yet how and to what extent kinase signaling affects splicing have not been defined on a genome-wide basis. Using a chemical genetic approach, we show in Schizosaccharomyces pombe that the SR protein kinase Dsk1 is required for efficient splicing of introns with suboptimal splice sites. Systematic substrate mapping in fission yeast and human cells revealed that SRPKs target evolutionarily conserved spliceosomal proteins, including the branchpoint-binding protein Bpb1 (SF1 in humans), by using an RXXSP consensus motif for substrate recognition. Phosphorylation of SF1 increases SF1 binding to introns with nonconsensus splice sites in vitro, and mutation of such sites to consensus relieves the requirement for Dsk1 and phosphorylated Bpb1 in vivo. Modulation of splicing efficiency through kinase signaling pathways may allow tuning of gene expression in response to environmental and developmental cues.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Lipp JJ,Marvin MC,Shokat KM,Guthrie Cdoi
10.1038/nsmb.3057subject
Has Abstractpub_date
2015-08-01 00:00:00pages
611-7issue
8eissn
1545-9993issn
1545-9985pii
nsmb.3057journal_volume
22pub_type
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