Diverse aberrancies target yeast mRNAs to cytoplasmic mRNA surveillance pathways

Abstract

Eukaryotic gene expression is a complex, multistep process that needs to be executed with high fidelity and two general methods help achieve the overall accuracy of this process. Maximizing accuracy in each step in gene expression increases the fraction of correct mRNAs made. Fidelity is further improved by mRNA surveillance mechanisms that degrade incorrect or aberrant mRNAs that are made when a step is not perfectly executed. Here, we review how cytoplasmic mRNA surveillance mechanisms selectively recognize and degrade a surprisingly wide variety of aberrant mRNAs that are exported from the nucleus into the cytoplasm.

Figure 1

Pathways of normal mRNA degradation. Normal mRNAs are degraded by two general mRNA degradation pathways. In the first pathway, following removal of the poly(A) tail, mRNAs are decapped by the Dcp1/2p complex and degraded by Xrn1p. In a second pathway, deadenylation is followed by degradation of the body of the mRNA from the 3’end by the exosome.

Figure 2

Model of nonstop mRNA degradation in yeast. Transcripts that lack all in-frame termination codons (nonstop mRNAs) cause the translating ribosome to stall at the 3’end of the message. The stalled ribosome is recognized by the C-terminal domain of Ski7p. The N-terminal domain of Ski7p recruits the exosome, providing a physical link between the nonstop mRNA and the exosome, which facilitates rapid degradation of the transcript. Nonstop mRNAs may also be translationally repressed, or the encoded protein may be targeted to the proteasome; however, the significance and mechanisms of these two aspects are not yet clear.

Figure 3

Model for no-go mRNA decay in yeast. Stem-loop structures, pseudoknots, and rare codons cause the translating ribosome to stall within the coding region of an mRNA. The stalled ribosome is recognized by the Hbs1p/Dom34p complex. Subsequently, the mRNA is cleaved endonucleolytically, generating 5’ and 3’ fragments that are degraded by the exosome and Xrn1p, respectively.

Figure 4

Unspliced and partially spliced mRNAs are exported and degraded in the cytoplasm. Pre-mRNAs can be exported into the cytoplasm where they are degraded either by nonsense-mediated decay, deadenylation-dependent decapping, or deadenylation-independent decapping. A 3’ splice-defective pre-mRNA containing a lariat structure at its 5’end is debranched in the nucleus by Dbr1p and exported to the cytoplasm where it is degraded by Xrn1p. Alternately, lariat structures can be exported to the cytoplasm and degraded by the exosome.