A brief survey of mRNA surveillance

Abstract

Defective mRNAs are degraded more rapidly than normal mRNAs in a process called mRNA surveillance. Eukaryotic cells use a variety of mechanisms to detect aberrations in mRNAs and a variety of enzymes to preferentially degrade them. Recent advances in the field of RNA surveillance have provided new information regarding how cells determine which mRNA species should be subject to destruction and novel mechanisms by which a cell tags an mRNA once such a decision has been reached. In this review, we highlight recent progress in our understanding of these processes.

Figure 1. Capping and decapping pathways

The 5' end of all RNA polymerase II transcripts is modified with a 7mGpppN cap. The required enzymes of the synthesis pathway are depicted in green. Either the fully formed cap or its precursors can be removed by various decapping enzymes (red). Alternatively, after the bulk of the transcript is degraded by an exonuclease, the residual ^7mGpppN cap structure can be degraded by the scavenging decapping enzyme (DcpS). For comparison, the bacterial RNA pyrophosphatase RppH (blue) is included.

Figure 2. Recognition of specific ribosomal states by eRF1/DOM34 and eRF3/Hbs1/Ski7

A. A ribosome with a normal stop codon in the A-site is recognized by eRF1–eRF3-GTP. GTP hydrolysis leads to release of the nascent peptide. B. A ribosome that is stalled at a sense codon in the A-site is recognized by Dom34–Hbs1-GTP. GTP hydrolysis leads to disassembly of the ribosome. Although the Dom34–Hbs1-GDP complex is depicted as being associated with the 60S subunit, this is not known. Instead, it might remain associated with the 40S subunit or be released. C. Genetic evidence suggests that a ribosome that is stalled at the end of an mRNA is recognized by Ski7. D. Termination at premature stop codons is aberrant. eRF1–eRF3-GTP can disassemble ribosomes if their capacity to hydrolyze the tRNA-peptide bond is blocked. This activity might have a role in nonsense-mediated decay. eRF1 and Dom34 are paralogs of each other, as are eRF3, Hbs1 and Ski7.

Figure 3. The Role of Uridylation in Eliciting Various Types of mRNA Decay

(i) In Arabidopsis thaliana, microRNA-mediated cleavage of mRNA targets results in an unadenylated but 5' capped product that is uridylated by a yet-to-be identified TUTase. (ii) The metazoan replication-dependent histone mRNAs are uridylated at the conclusion of S phase or under conditions of DNA replication inhibition. Several candidate TUTases have been shown to be involved in this event. (iii) Bulk mRNA turnover in Schizosaccharomyces pombe utilizes the TUTase Cid1, which adds a small number of uridines to the poly(A) tail to stimulate decay. All three types of mRNAs that attain oligo(U) tails may recruit the Lsm1-7 complex, which in turn recruits decapping enzymes including DCP2 and possibly NUDT16. The decapped message is then degraded by the 5' to 3' exonuclease XRN1.