A dual role for BBP/ScSF1 in nuclear pre-mRNA retention and splicing

AUTOR(ES)

Rutz, Berthold

FONTE

Oxford University Press

RESUMO

The MSL5 gene, which codes for the splicing factor BBP/ScSF1, is essential in Saccharomyces cerevisiae, yet previous analyses failed to reveal a defect in assembly of (pre)-spliceosomes or in vitro splicing associated with its depletion. We generated 11 temperature-sensitive (ts) mutants and one cold-sensitive (cs) mutant in the corresponding gene and analyzed their phenotypes. While all mutants were blocked in the formation of commitment complex 2 (CC2) at non-permissive and permissive temperature, the ts mutants showed no defect in spliceosome formation and splicing in vitro. The cs mutant was defective in (pre)-spliceosome formation, but residual splicing activity could be detected. In vivo splicing of reporters carrying introns weakened by mutations in the 5′ splice site and/or in the branchpoint region was affected in all mutants. Pre-mRNA leakage to the cytoplasm was strongly increased (up to 40-fold) in the mutants. A combination of ts mutants with a disruption of upf1, a gene involved in nonsense-mediated decay, resulted in a specific synthetic growth phenotype, suggesting that the essential function of SF1 in yeast could be related to the retention of pre-mRNA in the nucleus.

Documentos Relacionados

• A conditional U5 snRNA mutation affecting pre-mRNA splicing and nuclear pre-mRNA retention identifies SSD1/SRK1 as a general splicing mutant suppressor.
• Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing
• Evidence for a role for galectin-1 in pre-mRNA splicing.
• Human Splicing Factor SF3a, but Not SF1, Is Essential for Pre-mRNA Splicing In Vivo
• Pre-mRNA splicing and the nuclear matrix.