SMU-2 and SMU-1, Caenorhabditis elegans Homologs of Mammalian Spliceosome-Associated Proteins RED and fSAP57, Work Together To Affect Splice Site Choice
AUTOR(ES)
Spartz, Angela K.
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=444863Documentos Relacionados
- Specific protein-protein interactions between the essential mammalian spliceosome-associated proteins SAP 61 and SAP 114.
- Two protein–protein interaction sites on the spliceosome-associated human cyclophilin CypH
- The Mec-8 Gene of Caenorhabditis Elegans Affects Muscle and Sensory Neuron Function and Interacts with Three Other Genes: Unc-52, Smu-1 and Smu-2
- Analysis of smu-1, a Gene That Regulates the Alternative Splicing of unc-52 Pre-mRNA in Caenorhabditis elegans
- A novel set of spliceosome-associated proteins and the essential splicing factor PSF bind stably to pre-mRNA prior to catalytic step II of the splicing reaction.