Sen1p in Saccharomyces cerevisiae is a Type I DNA/RNA helicase. Mutations in the helicase domain perturb accumulation of diverse RNA classes, and Sen1p has been implicated in 3' end formation of non- coding RNAs. Mutations in the human ortholog of yeast SEN1 (SETX) have been implicated as a cause for the neurological disorders, ataxia-ocular apraxia 2 and Juvenile Amyotrophic Lateral Sclerosis (Lou Gehrig's disease). Speculation about the function of SETX in these diseases derives from work done on the yeast SEN1. Studies of sen1 mutants revealed defects in the processing of small nuclear RNA (snRNA).
The aims of this proposal focus on the functional analysis of the interaction between Sen1p and Rnt1p and Sen1p and SmDSp. Rnt1p, which resembles E. coli RNase III, is an endoribonuclease required for RNA maturation. SmDSp is a subunit of the splicing complex. To investigate the potential roles of these interactions in RNA processing, mutations will be created in SEN1 that specifically disrupt the Sen1p-Rnt1p or Sen1p-SmD3p interactions. To assess the purpose of these protein-protein interactions, the non-interacting mutants will be assayed to determine the effects of loss of interaction on processing of the U5 snRNA.
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| Zheng, Wei; Finkel, Jonathan S; Landers, Sharon M et al. (2008) Nonsense-mediated decay of ash1 nonsense transcripts in Saccharomyces cerevisiae. Genetics 180:1391-405 |
| Hume, Adam J; Finkel, Jonathan S; Kamil, Jeremy P et al. (2008) Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science 320:797-9 |
