In vivo effects on intron retention and exon skipping by the U2AF large subunit and SF1/BBP in the nematode Caenorhabditis elegans

  1. H. Robert Horvitz5,7
  1. 1State Key Laboratory of Medical Genetics, School of Biological Sciences and Technology, Central South University, Changsha, Hunan 410078, China
  2. 2Center for Clinical Gene Diagnosis and Therapy, The Second Xiangya Hospital, State Key Laboratory of Medical Genetics, Central South University, Changsha 410078, China
  3. 3Koch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts 02139, USA
  4. 4Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
  5. 5Department of Biology, Howard Hughes Medical Institute, MIT, Cambridge, Massachusetts 02139, USA
    1. 6 These authors contributed equally to this work.

    Abstract

    The in vivo analysis of the roles of splicing factors in regulating alternative splicing in animals remains a challenge. Using a microarray-based screen, we identified a Caenorhabditis elegans gene, tos-1, that exhibited three of the four major types of alternative splicing: intron retention, exon skipping, and, in the presence of U2AF large subunit mutations, the use of alternative 3′ splice sites. Mutations in the splicing factors U2AF large subunit and SF1/BBP altered the splicing of tos-1. 3′ splice sites of the retained intron or before the skipped exon regulate the splicing pattern of tos-1. Our study provides in vivo evidence that intron retention and exon skipping can be regulated largely by the identities of 3′ splice sites.

    Keywords

    Footnotes

    • Received March 23, 2011.
    • Accepted September 27, 2011.
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