Article

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

ABSTRACT

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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    • "Formation of the preinitiation complex involves specific recognition of the cap by eIF4E together with the translation factors eIF4G and eIF4A, which represents the rate limiting step of ribosome recruitment during the initiation of protein biosynthesis.3′-deadenylating enzyme678910, present primarily in vertebrates, that has been implicated in: i) maternal mRNA removal during embryogenesis and early development[11], ii) nonsense-mediated mRNA decay[2], iii) selection of mRNA for decay during cell motility regulation[12], iv) trimming of newly synthesized mRNAs[13]and small nucleolar RNAs[14], as well as v) miRNA maturation[15]. PARN deficiency in humans is linked to developmental delay and a number of telomere deficiency associated syndromes, such as idiopathic pulmonary fibrosis, dyskeratosis congenita and related haematological and neurological disorders161718. "
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    • "In addition , several types of stresses that induce eIF2 phosphorylation and translational repression promote SG formation and alter gene expression. A number of signaling pathways can also target various RNAbinding proteins (RBPs) that regulate mRNA stability and translation by promoting conventional or specific decay pathways such as NMD or ARE-mediated mRNA decay (Buchan and Parker, 2009; Schoenberg and Maquat, 2012; Venigalla and Turner, 2012). Several SG-associated RBPs undergo post-translational modifications such as phopshorylation, ubiquitination, N-acetyl glucosamination, methyl-argininylation and poly ADP-ribosylation, which in turn promote assembly of stalled mRNPs into SGs. "
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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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