Sen1 helicase is a transcription termination factor for RNA polymerase II.
Eric Steinmetz, David Brow
Biomolecular Chemistry, University of Wisconsin, 1300 University Ave, Madison, WI, 53706, USA
RNA polymerase II transcribes protein-coding genes as well as many non-coding genes. Termination of coding transcripts is coupled to pre-mRNA cleavage and polyadenylation, while termination of many non-coding transcripts utilizes a poly(A)-independent pathway requiring the RNA binding proteins Nrd1 and Nab3 and the probable RNA helicase Sen1. The mechanism of termination signal transmission to Pol II by either pathway is unknown. Several factors associated with the cleavage/polyadenylation factor CPF are important for both poly(A)-coupled and poly(A)-independent termination, suggesting that the two pathways may share a common signaling mechanism. We have extended this observation by uncovering a role for Sen1 in poly(A)-coupled termination. A mutation in Sen1's helicase motif that causes readthrough of snoRNA gene terminators also results in a severe defect in poly(A)-dependent termination, as revealed by transcription run-on analysis. This mutation does not affect pre-mRNA cleavage and polyadenylation, suggesting that Sen1 functions subsequent to mRNA 3'-processing factors in the termination pathway. Chromatin IP (ChIP) results reveal that Sen1 associates with the 3' regions of protein-coding genes, consistent with a direct role in termination. The discovery that a human homolog of Sen1, senataxin, is mutated in a newly identified form of ataxia suggests that defective termination of transcription or non-coding RNA biogenesis may underlie the disease state.
Return to YGM 2004 Home at SGD