RRC ID 6197
Author Campion Y, Neel H, Gostan T, Soret J, Bordonné R.
Title Specific splicing defects in S. pombe carrying a degron allele of the Survival of Motor Neuron gene.
Journal EMBO J
Abstract Spinal muscular atrophy results from deletions or mutations in the survival of motor neuron (SMN1) gene. The SMN protein has an essential role in the biogenesis of spliceosomal snRNPs, but the link between a defect in this process and specific splicing inhibition of pre-mRNAs has not been established. In this study, we report the construction of a temperature-degron (td) allele of the Schizosaccharomyces pombe SMN protein and show that its depletion at 37 degrees C affects splicing and formation of U1, U2, U4 and U5 snRNPs, but not of U6 and U3 ribonucleoproteins. The function of the tdSMN allele in snRNP assembly is already perturbed at 25 degrees C, suggesting a deleterious effect of the tag at this temperature. Using a genome-wide approach, we report that introns react unequally to lower levels of snRNPs in tdSMN cells and that increasing the length of the polypyrimidine tract can improve the splicing efficiency of some, but not all, affected introns. Altogether, our results suggest that the defects observed in tdSMN fission yeast cells mimic splicing deficits observed in SMN-deficient metazoan cells.
Volume 29(11)
Pages 1817-29
Published 2010-6-2
DOI 10.1038/emboj.2010.70
PII emboj201070
PMID 20400941
PMC PMC2885929
MeSH Alleles Cell Nucleus / genetics Cell Nucleus / metabolism Genes, Fungal* Humans Introns Motor Neurons / metabolism Muscular Atrophy, Spinal / genetics Muscular Atrophy, Spinal / metabolism Mutation RNA Precursors / genetics RNA Precursors / metabolism* RNA Splicing* Ribonucleoproteins / genetics Ribonucleoproteins / metabolism Ribonucleoproteins, Small Nuclear / genetics Ribonucleoproteins, Small Nuclear / metabolism* Schizosaccharomyces / genetics* Schizosaccharomyces pombe Proteins / genetics* Spliceosomes / genetics Spliceosomes / metabolism* Survival of Motor Neuron 1 Protein / genetics* snRNP Core Proteins
IF 9.889
Times Cited 35
DNA material S. pombe YFP-FLAG-His SpYFH19G10 (SPW087754)