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

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 m...

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Main Authors: Karen S Kim Guisbert, Hao Li, Christine Guthrie
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-01-01
Series:PLoS Biology
Online Access:http://europepmc.org/articles/PMC1717019?pdf=render
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author Karen S Kim Guisbert
Hao Li
Christine Guthrie
author_facet Karen S Kim Guisbert
Hao Li
Christine Guthrie
author_sort Karen S Kim Guisbert
collection DOAJ
description 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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spelling doaj.art-acb23e6d7b7745ac9cf7225809fcd00a2022-12-21T20:13:12ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852007-01-0151e610.1371/journal.pbio.0050006Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.Karen S Kim GuisbertHao LiChristine GuthrieThe 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.http://europepmc.org/articles/PMC1717019?pdf=render
spellingShingle Karen S Kim Guisbert
Hao Li
Christine Guthrie
Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.
PLoS Biology
title Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.
title_full Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.
title_fullStr Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.
title_full_unstemmed Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.
title_short Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.
title_sort alternative 3 pre mrna processing in saccharomyces cerevisiae is modulated by nab4 hrp1 in vivo
url http://europepmc.org/articles/PMC1717019?pdf=render
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