P-Bodies React to Stress and Nonsense

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P-Bodies React to Stress and Nonsense Ivone Bruno, Miles F. Wilkinson  Cell  Volume 125, Issue 6, Pages 1036-1038 (June 2006) DOI: 10.1016/j.cell.2006.06.003 Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 1 The Active Lives of P-Bodies (Left) Two RNA regulatory pathways converge in P-bodies. MicroRNAs are processed from primary miRNAs in the nucleus and are further cleaved in the cytoplasm to form an miRNA ribonucleoprotein (miRNP) complex. This complex represses the translation of specific mRNAs by base pairing with their 3′UTRs. Bhattacharyya et al. (2006) provide evidence that the miRNA miR-122 represses the translation of the cationic amino acid transporter-1 (CAT-1) mRNA in P-bodies. Stress relieves this repression, releasing CAT-1 mRNA from P-bodies and allowing its active translation. The derepression of CAT-1 translation requires HuR, an RNA binding protein that interacts with AU-rich elements (AREs) in the 3′UTR of CAT-1. Because HuR is a nuclear-cytoplasmic shuttling protein it may be recruited to CAT-1 mRNA when it is first made in the nucleus. Alternatively, HuR may be recruited to CAT-1 mRNA in the cytoplasm in response to stress, as some stresses are known to mobilize HuR to the cytoplasm. 7mG is a specialized 5′ cap found on mRNAs, and AAA represents the polyadenosine tail found on most mRNAs. (Right) According to Sheth and Parker (2006), P-bodies are sites where aberrant mRNAs harboring premature termination (nonsense) codons are degraded by an RNA surveillance pathway called nonsense-mediated decay (NMD). Recruitment of PTC-bearing mRNAs to P-bodies requires UPF1, an ATPase-dependent RNA helicase essential for NMD. Entry into the P-body is not sufficient for mRNA decay; also required is UPF1 ATP hydrolysis and ill-defined steps mediated by the NMD proteins UPF2 and UPF3. Some normal mRNAs are also present in P-bodies, where they may be stored as translationally repressed mRNAs. Normal mRNAs can also exit P-bodies to be translated, a process that evidence from Sheth and Parker (2006) indicates requires UPF1-mediated ATP hydrolysis. Cell 2006 125, 1036-1038DOI: (10.1016/j.cell.2006.06.003) Copyright © 2006 Elsevier Inc. Terms and Conditions