P‐bodies and their functions during mRNA cell cycle: Mini‐review

P‐bodies (processing bodies) are observed in different organisms such as yeast, Caenorhabditis elegans and mammals. A typical eukaryotic cell contains several types of spatially formed granules, such as P‐bodies, stress granules and a variety of ribonucleoprotein bodies. These microdomains play important role in mRNA processing, including RNA interference, repression of translation and mRNA decay. The P‐bodies components as well as stress granules may play an important role in host defense against viral infection. The complete set of P‐bodies protein elements is still poor known. They contain conserved protein core limited to different organisms or to stress status of the cell. P‐bodies are related also to some neuronal mRNA granules as well as to maternal RNA granules or male germ cell granules. In this mini‐review, we focus on the structure of P‐bodies and their function in the mRNA utilization and processing because of the high mRNA's dynamics between different cellular compartments and its key role in modulation of gene expression. Copyright © 2012 John Wiley & Sons, Ltd.     

RNA metabolism: putting the brake on the UPR

The unfolded protein response (UPR) is a major signaling cascade that determines cell fate under conditions of endoplasmic reticulum (ER) stress. The kinetics and amplitude of UPR responses are tightly controlled by several feedback loops and the expression of positive and negative regulators. In this issue of EMBO Reports, the Wilkinson lab uncovers a novel function of nonsense‐mediated RNA decay (NMD) in fine‐tuning the UPR 1 . NMD is an mRNA quality control mechanism known to destabilize aberrant mRNAs that contain premature termination codons. In this work, NMD was shown to determine the threshold of stress necessary to activate the UPR, in addition to adjusting the amplitude of downstream responses and the termination phase. These effects were mapped to the control of the mRNA stability of IRE1, a major ER stress transducer. This study highlights the dynamic crosstalk between mRNA metabolism and the proteostasis network demonstrating the physiological relevance of normal mRNA regulation by the NMD pathway.     

Post-transcriptional control of gene expression: bacterial mRNA degradation

Many biological processes cannot be fully understood without detailed knowledge of RNA metabolism. The continuous breakdown and resynthesis of prokaryotic mRNA permit rapid production of new kinds of proteins. In this way, mRNA levels can regulate protein synthesis and cellular growth. Analysing mRNA degradation in prokaryotes has been particularly difficult because most mRNA undergo rapid exponential decay. Prokaryotic mRNAs differ in their susceptibility to degradation by endonucleases and exonucleases, possibly because of variation in their sequencing and structure. In spite of numerous studies, details of mRNA degradation are still largely unknown. This review highlights those aspects of mRNA metabolism which seem most influential in the regulation of gene expression.     

Messenger RNA Turnover in Eukaryotes: Pathways and Enzymes

The control of mRNA degradation is an important component of the regulation of gene expression since the steady-state concentration of mRNA is determined both by the rates of synthesis and of decay. Two general pathways of mRNA decay have been described in eukaryotes. Both pathways share the exonucleolytic removal of the poly(A) tail (deadenylation) as the first step. In one pathway, deadenylation is followed by the hydrolysis of the cap and processive degradation of the mRNA body by a 5′ exonuclease. In the second pathway, the mRNA body is degraded by a complex of 3′ exonucleases before the remaining cap structure is hydrolyzed. This review discusses the proteins involved in the catalysis and control of both decay pathways.     

Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment

Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA‐induced silencing complex (RISC), with target p21 mRNA via binding of the stem‐loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA‐mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA‐mediated gene silencing. In addition, these findings indicate that fine‐tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence.