The Search for Trans-Acting Factors Controlling Messenger RNA Decay

Gerald M. Wilson, Gary Brewer

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Control of mRNA turnover is an integral component of regulated gene expression. Individual mRNAs display a wide range of stabilities, which in many cases have been linked to discrete sequence elements. The most extensively characterized determinants of rapid constitutive mRNA turnover in mammalian systems are A + U-rich elements (AREs), first identified in the 3′ untranslated regions of many cytokine/lymphokine and protooncogene mRNAs. In this article, we describe recent advances in the characterization of ARE-directed mRNA turnover, including links to deadenylation kinetics and functional heterogeneity among AREs from different mRNAs. We then describe strategies employed in the search for trans-acting factors interacting with these elements. Using such techniques, an ARE-binding activity capable of accelerating c-myc mRNA turnover in vitro was identified, and named AUF1. Subsequent cloning and characterization revealed that AUF1 exists as a family of four proteins formed by alternative splicing of a common pre-mRNA and appears to function as part of a multisubunit trans-acting complex to promote ARE-directed mRNA turnover. Investigations using several systems have demonstrated that AUF1 expression and/or activity correlate with rapid decay of ARE-containing mRNAs, and that both expression and activity of AUF1 are regulated by developmental and signal transduction mechanisms.

Original languageEnglish (US)
Pages (from-to)257-291
Number of pages35
JournalProgress in nucleic acid research and molecular biology
Volume62
Issue numberC
DOIs
StatePublished - Jan 1 1998

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Trans-Activators
RNA Stability
Messenger RNA
Lymphokines
RNA Precursors
Alternative Splicing
3' Untranslated Regions
Organism Cloning
Signal Transduction
Cytokines
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Cite this

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The Search for Trans-Acting Factors Controlling Messenger RNA Decay. / Wilson, Gerald M.; Brewer, Gary.

In: Progress in nucleic acid research and molecular biology, Vol. 62, No. C, 01.01.1998, p. 257-291.

Research output: Contribution to journalArticle

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