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Protein-mediated Translational Repression

Kristine M. Campbell, Gary D. Stormo, Larry Gold


Regulation of protein synthesis at the level of translation is one of the many ways cells control the concentrations of gene products. We define (for this review) translational regulation to be the variation from “constitutive” levels of translation caused by the action of specific proteins on specific mRNAs. The constitutive efficiencies of translation of mRNAs are determined by both the sequence and the structure of their initiation regions (Steitz 1979; Gold et al. 1981; Stormo et al. 1982). mRNAs are in excess of ribosomes; i.e., free ribosomes are less abundant than are open initiation regions on mRNA. Selection of messages for translation occurs according to the relative strengths of their initiation domains. Primary sequence features important for recognition by ribosomes include the polypurine Shine and Dalgarno region, the initiation codon, and other nearby nucleotides (Gold et al. 1981). Initiation regions possess varying degrees of structure, from the unstructured T4 gene-32 message to the obviously structured MS2 replicase message (see below).

The features of mRNAs recognized by translational regulatory proteins include both sequence and structure. The role of structure in mRNA function is often overlooked but is of prime importance to translational regulation. Work on tRNA structure and function (Altman 1978), the autocatalytic splicing of Tetrahymena ribosomal (r)RNA (Kruger et al. 1982), mRNA attenuation regions (see Bauer et al., this volume), and the role of RNA in RNase P activity (Reed et al. 1982) suggest that the relationship between RNA structure and function is complex.

In this paper we discuss...

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