Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 49, Pages 17675-17680Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503803102
Keywords
cis-regulatory element; gene expression; microarray; mRNA decay; Puf protein
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Funding
- NHGRI NIH HHS [R01 HG003008, HG003008] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008798, GM63759, R01 GM063759, GM008798] Funding Source: Medline
- NLM NIH HHS [P20 LM007276, LM007276] Funding Source: Medline
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The steady-state abundance of an mRNA is determined by the balance between transcription and decay. Although regulation of transcription has been well studied both experimentally and computationally, regulation of transcript stability has received little attention. We developed an algorithm, MatrixREDUCE, that discovers the position-specific affinity matrices for unknown RNA-binding factors and infers their condition-specific activities, using only genomic sequence data and steady-state mRNA expression data as input. We identified and computationally characterized the binding sites for six mRNA stability regulators in Saccharomyces cerevisiae, which include two members of the Pumilio-homology domain (Puf) family of RNA-binding proteins, Puf3p and Puf4p. We provide computational and experimental evidence that regulation of mRNA stability by these factors is modulated in response to a variety of environmental stimuli.
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