Specific commitment of different pre-mRNAs to splicing by single SR proteins.
Higher eukaryotic cells express a family of essential splicing factors with a characteristic RNA-binding domain and serine/arginine-rich (SR) motif. These SR proteins, which include SC35 and SF2/ASF, are conserved from Drosophila to man, are required for early steps of spliceosome assembly and can influence splice-site selections. To address their mechanisms of action, SR proteins were examined for their role in committing pre-messenger RNA to the splicing pathway. I report here that SC35 was sufficient on its own to form a committed complex with human beta-globin pre-mRNA. Examination of other SR proteins and pre-mRNA substrates revealed that single SR proteins committed different pre-mRNAs to splicing with pronounced substrate specificity. These results suggest that splicing of different pre-mRNAs may require distinct sets of SR proteins, and that the commitment by SR proteins may be a critical step at which alternative and tissue-specific splicing is regulated.
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Division of Cellular and Molecular Medicine, University of California at San Diego, La Jolla 92093-0651.
D000818:Animals; D016367:Baculoviridae; D001667:Binding, Competitive; D002460:Cell Line; D003001:Cloning, Molecular; D015696:Gene Products, tat / Q000235:genetics; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D009036:Moths; D009687:Nuclear Proteins / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000378:metabolism
D015696:Gene Products, tat; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D005914:Globins