Regulation of cytoplasmic mRNA decay

Department of Molecular and Cellular Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210, USA.
Nature Reviews Genetics (Impact Factor: 36.98). 03/2012; 13(4):246-59. DOI: 10.1038/nrg3160
Source: PubMed


Discoveries made over the past 20 years highlight the importance of mRNA decay as a means of modulating gene expression and thereby protein production. Up until recently, studies largely focused on identifying cis-acting sequences that serve as mRNA stability or instability elements, the proteins that bind these elements, how the process of translation influences mRNA decay and the ribonucleases that catalyse decay. Now, current studies have begun to elucidate how the decay process is regulated. This Review examines our current understanding of how mammalian cell mRNA decay is controlled by different signalling pathways and lays out a framework for future research.

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    • "Once transcription stops at the end of the growth phase, control of gene expression becomes posttranscriptional until ZGA and involves regulation of mRNA translation, exemplified by recruitment of maternal mRNAs discussed above, and regulation of mRNA stability. mRNA degradation (reviewed in Balagopal, Fluch, & Nissan, 2012; Houseley & Tollervey, 2009; Schoenberg & Maquat, 2012) usually involves deadenylation of the 3 0 -poly(A) tail and/or decapping. In mammalian somatic cells, deadenylation coupled with decapping is the main mRNA decay pathway (Yamashita et al., 2005). "
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    • "and deadenylases (Hoefig et al., 2013; Schoenberg and Maquat, 2012). Knockdown of deadenylases and the exosome subunit EXOSC10 yielded inconsistent results in preliminary studies. "
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    • "To test this, we used cells isolated from FSHD1 (54-2, which are isogenic to normal 54-1 cells but carry a contracted D4Z4 array) and FSHD2 (MB200) skeletal muscle (Krom et al., 2012; Schoenberg and Maquat, 2012; Young et al., 2013). We knocked down UFP1 in 54-2 and MB200 myoblasts to 24.3% and 32.4% of normal protein levels, respectively, and differentiated these myoblasts to myotubes to stimulate DUX4 transcription. "
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