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

Autor: Karen S Kim Guisbert, Hao Li, Christine Guthrie
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: PLoS Biology, Vol 5, Iss 1, p e6 (2007)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.0050006
Popis: 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.
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