mRNA Turnover


Messenger ribonucleic acid (mRNA) degradation mechanisms provide important regulatory steps in the control of eukaryotic gene expression. Although major recent advances have been made in our understanding of cytoplasmic mRNA turnover in mammalian cells, we are only just beginning to unravel the mechanisms of RNA turnover in the cell nucleus.

Keywords: exonuclease; exosome; nonsense‐mediated decay; deadenylase; RNA helicase

Figure 1.

General messenger ribonucleic acid (mRNA) decay pathways in eukaryotes. Deadenylation in yeast is carried out by the Ccr4p/Caf1p complex. A homologous complex is present in mammalian cells, as well as the PARN deadenylase. In the 5′ decay pathway, deadenylation is followed by Dcp1p‐mediated decapping and 5′→3′ exonucleolytic degradation by Xrn1p. In the 3′ decay pathway, the exosome complex of 3′→5′ exonucleases, Ski7p and the Ski complex mediate the 3′→5′ degradation of the deadenylated mRNA. After the exosome has completely degraded the mRNA, the released cap structure is cleaved by DcpS. The 5′ decay pathway is the major mechanism in yeast, whereas mammalian cells predominantly use the 3′ decay pathway.

Figure 2.

Model for messenger ribonucleic acid (mRNA) surveillance. mRNA processing events in the nucleus dictate the mRNP structure, exon junction complexes (EJC) indicating the location of spliced sites. Since introns are normally found within the coding regions of genes, the EJCs are normally displaced by the elongating ribosome in the initial round of translation. Translation elongation ceases at a normal stop codon or a premature termination codon (PTC). A surveillance complex (SC) consisting of the Upf factors is assembled by sequential interactions with the release factors (RF) and scans downstream of the stop codon. If the surveillance complex encounters an EJC, the termination event is judged to be premature. The mRNA is degraded by decapping and 5′→3′ exonucleolytic activity. In yeast, where only a few mRNAs contain introns, the nonsense‐mediated decay (NMD) function of the EJC is replaced by the hnRNP protein Hrp1p, which binds to degenerate sites within yeast open reading frames.



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Further Reading

Brouwer R, Pruijn GJM and van Venrooij WJ (2000) The human exosome: an autoantigenic complex of exoribonucleases in myositis and scleroderma. Arthritis Research 3: 102–106.

Coller JM, Tucker M, Sheth U, Valencia‐Sanchez MA and Parker R (2001) The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA 7: 1717–1727.

Gonzalez CI, Bhattacharya A, Wang W and Peltz SW (2001) Nonsense‐mediated mRNA decay in Saccharomyces cerevisiae. Gene 274: 15–25.

Jackson DA, Pombo A and Iborra F (2000) The balance sheet for transcription: an analysis of nuclear RNA metabolism in mammalian cells. FASEB Journal 14: 242–254.

Jensen TH, Patricio K, McCarthy T and Rosbash M (2001) A block to mRNA export in Saccharomyces cerevisiae leads to hyperadenylation of transcripts that accumulate at the site of transcription. Molecular Cell 7: 887–898.

Le Hir H, Gatfield D, Izaurralde E and Moore MJ (2001) The exon–exon junction complex provides a binding platform for factors involved in mRNA export and nonsense‐mediated mRNA decay. EMBO Journal 20: 4987–4997.

Maquat LE and Carmichael GG (2001) Quality control of mRNA function. Cell 104: 173–176.

Mitchell P and Tollervey D (2000) Musing on the structural organization of the exosome complex. Nature Structural Biology 7: 843–846.

Mitchell P and Tollervey D (2001) mRNA turnover. Current Opinion in Cell Biology 13: 320–325.

Shyu A‐B and Wilkinson MF (2000) The double lives of shuttling mRNA binding proteins. Cell 102: 135–138.

Tucker M and Parker R (2000) Mechanisms and control of mRNA decapping in Saccharomyces cerevisiae. Annual Review of Biochemistry 69: 571–595.

Wilusz CJ, Wang W and Peltz SW (2001) Curbing the nonsense: the activation and regulation of mRNA surveillance. Genes and Development 15: 2781–2785.

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Mitchell, Philip(Sep 2006) mRNA Turnover. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005981]