SMU-2 and SMU-1, Caenorhabditis elegans Homologs of Mammalian Spliceosome-Associated Proteins RED and fSAP57, Work Together To Affect Splice Site Choice
- 1 August 2004
- journal article
- research article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 24 (15) , 6811-6823
- https://doi.org/10.1128/mcb.24.15.6811-6823.2004
Abstract
Mutations in the Caenorhabditis elegans gene smu-2 suppress mec-8 and unc-52 mutations. It has been proposed that MEC-8 regulates the alternative splicing of unc-52 transcripts, which encode the core protein of perlecan, a basement membrane proteoglycan. We show that mutation in smu-2 leads to enhanced accumulation of transcripts that skip exon 17, but not exon 18, of unc-52, which explains our finding that smu-2 mutations suppress the uncoordination conferred by nonsense mutations in exon 17, but not in exon 18, of unc-52. We conclude that smu-2 encodes a ubiquitously expressed nuclear protein that is 40% identical to the human RED protein, a component of purified spliceosomes. The effects of smu-2 mutation on both unc-52 pre-mRNA splicing and the suppression of mec-8 and unc-52 mutant phenotypes are indistinguishable from the effects of mutation in smu-1, a gene that encodes a protein that is 62% identical to human spliceosome-associated protein fSAP57. We provide evidence that SMU-2 protects SMU-1 from degradation in vivo. In vitro and in vivo coimmunoprecipitation experiments indicate that SMU-2 and SMU-1 bind to each other. We propose that SMU-2 and SMU-1 function together to regulate splice site choice in the pre-mRNAs of unc-52 and other genes.Keywords
This publication has 71 references indexed in Scilit:
- Chromosome cohesion is regulated by a clock gene paralogue TIM-1Nature, 2003
- Correction of disease-associated exon skipping by synthetic exon-specific activatorsNature Structural & Molecular Biology, 2003
- A Unique Glutamic Acid-Lysine (EK) Domain Acts as a Splicing InhibitorJournal of Biological Chemistry, 2002
- Splicing Regulation at the Second Catalytic Step by Sex-lethal Involves 3′ Splice Site Recognition by SPF45Cell, 2002
- Analysis of smu-1, a Gene That Regulates the Alternative Splicing of unc-52 Pre-mRNA in Caenorhabditis elegansMolecular and Cellular Biology, 2001
- Expression of Spliceosome-Associated Protein 49 Is Required for Early Embryogenesis inCaenorhabditis elegansBiochemical and Biophysical Research Communications, 1998
- Chapter 19 DNA TransformationPublished by Elsevier ,1995
- A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans.Genes & Development, 1987
- A mutation in Caenorhabditis elegans that increases recombination frequency more than threefoldNature, 1979
- Muscle development in Caenorhabditis elegans: Mutants exhibiting retarded sarcomere constructionCell, 1978