Posttranscriptional Control of Gene Expression in Yeast

Abstract

SUMMARY Studies of the budding yeast Saccharomyces cerevisiae have greatly advanced our understanding of the posttranscriptional steps of eukaryotic gene expression. Given the wide range of experimental tools applicable to S. cerevisiae and the recent determination of its complete genomic sequence, many of the key challenges of the posttranscriptional control field can be tackled particularly effectively by using this organism. This article reviews the current knowledge of the cellular components and mechanisms related to translation and mRNA decay, with the emphasis on the molecular basis for rate control and gene regulation. Recent progress in characterizing translation factors and their protein-protein and RNA-protein interactions has been rapid. Against the background of a growing body of structural information, the review discusses the thermodynamic and kinetic principles that govern the translation process. As in prokaryotic systems, translational initiation is a key point of control. Modulation of the activities of translational initiation factors imposes global regulation in the cell, while structural features of particular 5′ untranslated regions, such as upstream open reading frames and effector binding sites, allow for gene-specific regulation. Recent data have revealed many new details of the molecular mechanisms involved while providing insight into the functional overlaps and molecular networking that are apparently a key feature of evolving cellular systems. An overall picture of the mechanisms governing mRNA decay has only very recently begun to develop. The latest work has revealed new information about the mRNA decay pathways, the components of the mRNA degradation machinery, and the way in which these might relate to the translation apparatus. Overall, major challenges still to be addressed include the task of relating principles of posttranscriptional control to cellular compartmentalization and polysome structure and the role of molecular channelling in these highly complex expression systems.

Polycistronic gene expression in yeast versus cryptic promoter elements

“…For reinitiation, the ribosome does not dissociate after passing the stop codon, it rather scans back and forth until a new initiation site is found. This mechanism resembles eukaryotic scanning ( [1,2] and references therein). Alternatively, recruitment of new ribosomes (de novo initiation) can occur either at a Shine^Dalgarno region or at recently discussed so-called 'downstream boxes' [3].…”

“…Initiation of translation of the majority of cellular mRNAs in mammalian systems occurs by the so-called scanning model [4^6], which with some modi¢cations also holds true for translation of yeast cellular genes (for review see [1,2,7] and references therein). The eukaryotic mRNA is modi¢ed after transcription while still in the nucleus : the cap structure is added at the 5P end and a stretch of up to 200 adenylate residues is attached to the 3P end.…”

Pushing the limits of the scanning mechanism for initiation of translation

“…Scanning appears to be dependent on ATP hydrolysis (Kozak, 1980), thereby implicating eIF4A, an RNA-dependent ATPase which might control the hypothetical clamp. Some ideas about the function of other initiation factors are reviewed elsewhere (Dever, 2002;McCarthy, 1998;Pestova et al, 2001).…”

Tetracycline‐aptamer‐mediated translational regulation in yeast

“…Translational regulation constitutes an important point of post-transcriptional control of gene expression, enabling the cell to change rapidly the level of gene product (Mathews et al ., 2000). Translation is mainly regulated at the step of initiation (Yoon and Donahue, 1992;Kaufman, 1994;Gray and Wickens, 1998;McCarthy, 1998). The cap structure at the 5 ¢ end of the mRNA facilitates the recruitment of the 43S preinitiation complex (Sonenberg, 1994).…”