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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Available from: Daniel R Schoenberg
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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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    ABSTRACT: The mRNA 5′ cap structure plays a pivotal role in coordination of eukaryotic translation and mRNA degradation. Poly(A)-specific ribonuclease (PARN) is a dimeric exoribonuclease that efficiently degrades mRNA 3′ poly(A) tails while also simultaneously interacting with the mRNA 5′ cap. The cap binding amplifies the processivity of PARN action. We used surface plasmon resonance kinetic analysis, quantitative equilibrium fluorescence titrations and circular dichroism to study the cap binding properties of PARN.
    Full-text · Article · Jan 2016 · Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics
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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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    ABSTRACT: Messenger RNA (mRNA) turnover that determines the lifetime of cytoplasmic mRNAs is a means to control gene expression under both normal and stress conditions, whereas its impact on ageing and age-related disorders has just become evident. Gene expression control is achieved at the level of the mRNA clearance as well as mRNA stability and accessibility to other molecules. All these processes are regulated by cis-acting motifs and trans-acting factors that determine the rates of translation and degradation of transcripts. Specific messenger RNA granules that harbor the mRNA decay machinery or various factors, involved in translational repression and transient storage of mRNAs, are also part of the mRNA fate regulation. Their assembly and function can be modulated to promote stress resistance in adverse conditions and over time affect the ageing process and the lifespan of the organism. Here, we provide insights into the complex relationships of ageing modulators and mRNA turnover mechanisms.
    Full-text · Article · Oct 2015 · Mechanisms of ageing and development
    • "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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    ABSTRACT: In mouse, the oocyte-to-embryo transition entails converting a highly differentiated oocyte to totipotent blastomeres. This transition is driven by degradation of maternal mRNAs, which results in loss of oocyte identity, and reprogramming of gene expression during the course of zygotic gene activation, which occurs primarily during the two-cell stage and confers blastomere totipotency. Full-grown oocytes are transcriptionally quiescent and mRNAs are remarkably stable in oocytes due to the RNA-binding protein MSY2, which stabilizes mRNAs, and low activity of the 5' and 3' RNA degradation machinery. Oocyte maturation initiates a transition from mRNA stability to instability due to phosphorylation of MSY2, which makes mRNAs more susceptible to the RNA degradation machinery, and recruitment of dormant maternal mRNAs that encode for critical components of the 5' and 3' RNA degradation machinery. Small RNAs (miRNA, siRNA, and piRNA) play little, if any, role in mRNA degradation that occurs during maturation. Many mRNAs are totally degraded but a substantial fraction is only partially degraded, their degradation completed by the end of the two-cell stage. Genome activation initiates during the one-cell stage, is promiscuous, low level, and genome wide (and includes both inter- and intragenic regions) and produces transcripts that are inefficiently spliced and polyadenylated. The major wave of genome activation in two-cell embryos involves expression of thousands of new genes. This unique pattern of gene expression is the product of maternal mRNAs recruited during maturation that encode for transcription factors and chromatin remodelers, as well as dramatic changes in chromatin structure due to incorporation of histone variants and modified histones.
    No preview · Article · Sep 2015 · Current Topics in Developmental Biology
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