SR protein kinases promote splicing of nonconsensus introns
| Autor: | Jesse J. Lipp, Michael C. Marvin, Kevan M. Shokat, Christine Guthrie |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Ribonucleoprotein
U4-U6 Small Nuclear RNA Splicing Amino Acid Motifs Blotting Western Protein Serine-Threonine Kinases Proteomics Substrate Specificity Splicing factor SR protein Structural Biology Schizosaccharomyces Amino Acid Sequence Phosphorylation Molecular Biology Oligonucleotide Array Sequence Analysis Genetics Reverse Transcriptase Polymerase Chain Reaction Kinase Chemistry Intron Introns Cell biology Mutation RNA splicing RNA Splice Sites RNA Splicing Factors Schizosaccharomyces pombe Proteins Chemical genetics |
| Zdroj: | Nature Structural & Molecular Biology. 22:611-617 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.3057 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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