Co-translational mRNA decay in Saccharomyces cerevisiae

Abstract

The rates of RNA decay and transcription determine the steady state levels of all mRNAs and both can be subject to regulation. While the details of transcriptional regulation are becoming increasingly understood, the mechanism(s) controlling mRNA decay remain unclear. In yeast, a major pathway of mRNA decay begins with deadenylation followed by decapping and 5’-3’ exonuclease digestion. Importantly, it is hypothesized that ribosomes must be removed from mRNA before transcripts are destroyed. Contrary to this prediction, here we show that decay takes place while mRNAs are associated with actively translating ribosomes. The data indicate that dissociation of ribosomes from mRNA is not a prerequisite for decay and we suggest that the 5’-3’ polarity of mRNA degradation has evolved to ensure that the last translocating ribosome can complete translation.

General and MicroRNA-Mediated mRNA Degradation Occurs on Ribosome Complexes in Drosophila Cells

“…However, with the finding of cytoplasmic P bodies, which accumulate, e.g., factors of the general mRNA degradation pathway but no ribosomes, it was proposed that mRNA decapping could occur only in P bodies after dissociation of the mRNA from ribosomes (11,(37)(38)(39)(40)(41)(42). More recently, Coller and coworkers provided additional experimental evidence to support the initial hypothesis of cotranslational degradation of some mRNAs in yeast (43,44). In this study, we significantly extend the experimental support for the hypothesis that the ribosome is a very general site not only for general 5=-to-3= mRNA degradation in Drosophila but also for the miRNA-mediated mRNA degradation pathway.…”

“…Therefore, it was postulated that mRNA decapping would require the dissociation of the mRNA from the ribosome followed by their accumulation in P bodies (11,(37)(38)(39)(40)(41)(42). In contrast, more recently Hu et al (43,44) have shown decapped degradation intermediates of several mRNAs, vector with a 3ϫ Flag sequence downstream of the metallothionein promoter in the pMK33/pMTHy backbone, followed in frame by a gateway cassette (Life Technologies), was constructed. The E. coli BirA ligase was PCR amplified and recombined into the pDONR221 plasmid.…”

Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation

“…The main axes of the ellipses reveal that the errors in the estimation of synthesis and decay rates are not independent, yet small enough to prove that the coupling is not due to estimation variance. Brengues et al 2005;Hu et al 2009). There is also evidence that nuclear and cytoplasmic mRNA metabolism are linked.…”

“…During transcription, the mRNA receives a 59-cap and a 39-poly(A) tail. The mature mRNA is then exported to the cytoplasm, translated, and eventually degraded cotranslationally (Hu et al 2009). Cytoplasmic mRNA degradation generally begins with shortening of the poly(A) tail by the Ccr4-Not complex, which contains the deadenylases Ccr4 and Pop2 (also known as Caf1) (Liu et al 1998;Tucker et al 2001).…”

Translation by Ribosomes with mRNA Degradation: Exclusion Processes on Aging Tracks

“…First, the initiation region is decapped to prevent the assembly of new ribosomes. Second, the ribosomes present on the mRNA at the moment of decapping are allowed to finish their translation [9,14]. While degradation of mRNA before completion of protein production looks like a wasteful process at first sight, it is also a control mechanism that enhances the efficiency of protein synthesis [15].…”