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PLoS Biol. 2007 Jan;5(1):e6.

Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.

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  • 1Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.

Abstract

The Saccharomyces cerevisiae RNA-binding protein Nab4/Hrp1 is a component of the cleavage factor complex required for 3' pre-mRNA processing. Although the precise role of Nab4/Hrp1 remains unclear, it has been implicated in correct positioning of the cleavage site in vitro. Here, we show that mutation or overexpression of NAB4/HRP1 alters polyA cleavage site selection in vivo. Using bioinformatic analysis, we identified four related motifs that are statistically enriched in Nab4-associated transcripts; each motif is similar to the known binding site for Nab4/Hrp1. Site-directed mutations in predicted Nab4/Hrp1 binding elements result in decreased use of adjacent cleavage sites. Additionally, we show that the nab4-7 mutant displays a striking resistance to toxicity from excess copper. We identify a novel target of alternative 3' pre-mRNA processing, CTR2, and demonstrate that CTR2 is required for the copper resistance phenotype in the nab4-7 strain. We propose that alternative 3' pre-mRNA processing is mediated by a Nab4-based mechanism and that these alternative processing events could help control gene expression as part of a physiological response in S. cerevisiae.

PMID:
17194212
[PubMed - indexed for MEDLINE]
PMCID:
PMC1717019
Free PMC Article

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