Profiling condition-specific, genome-wide regulation of mRNA stability in yeast

Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17675-80. doi: 10.1073/pnas.0503803102. Epub 2005 Nov 29.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal / genetics*
  • Genome, Fungal / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Protein Folding
  • Protein-Serine-Threonine Kinases
  • RNA Stability / genetics*
  • RNA Stability / physiology*
  • RNA-Binding Proteins / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction

Substances

  • PUF4 protein, S cerevisiae
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein-Serine-Threonine Kinases
  • target of rapamycin protein, S cerevisiae