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Pat1 RNA‐binding proteins: Multitasking shuttling proteins

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Abstract Post‐transcriptional regulation of gene expression is largely achieved at the level of splicing in the nucleus, and translation and mRNA decay in the cytosol. While the regulation may be global, through the direct inhibition of central factors, such as the spliceosome, translation initiation factors and mRNA decay enzymes, in many instances transcripts bearing specific sequences or particular features are regulated by RNA‐binding factors which mobilize or impede recruitment of these machineries. This review focuses on the Pat1 family of RNA‐binding proteins, conserved from yeast to man, that enhance the removal of the 5′ cap by the decapping enzyme Dcp1/2, leading to mRNA decay and also have roles in translational repression. Like Dcp1/2, other decapping coactivators, including DDX6 and Edc3, and translational repressor proteins, Pat1 proteins are enriched in cytoplasmic P‐bodies, which have a principal role in mRNA storage. They also concentrate in nuclear Cajal‐bodies and splicing speckles and in man, impact splice site choice in some pre‐mRNAs. Pivotal to these functions is the association of Pat1 proteins with distinct heptameric Lsm complexes: the cytosolic Pat1/Lsm1‐7 complex mediates mRNA decay and the nuclear Pat1/Lsm2‐8 complex alternative splicing. This dual role of human Pat1b illustrates the power of paralogous complexes to impact distinct processes in separate compartments. The review highlights our recent findings that Pat1b mediates the decay of AU‐rich mRNAs, which are particularly enriched in P‐bodies, unlike the decapping activator DDX6, which acts on GC‐rich mRNAs, that tend to be excluded from P‐bodies, and discuss the implications for mRNA decay pathways. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNRNA Processing > Splicing Regulation/Alternative Splicing Translation > Translation Regulation
Pat1 proteins. (a) Table of Pat1 proteins with names and length in amino acids. (b) Cartoon indicating the differential expression of xPat1a and xPat1b during Xenopus oogenesis and embryogenesis
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Summary model of Pat1b's functions in cytoplasmic mRNA decay and nuclear alternative splicing, via Lsm1‐7 and Lsm2‐8, respectively
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Pat1b tends to degrade AU‐rich mRNAs which are resident in P‐bodies, unlike DDX6 which decays GC‐rich mRNAs. (a) mRNA enrichment in P‐bodies purified from nonstressed HEK293 cells (Hubstenberger et al. ) was expressed as a function of mRNA fold‐changes after PAT1B silencing (Vindry et al. ). All mRNAs (14730) are in gray, while mRNAs with a GC content lower than 40% (2124) are in red. (b) mRNAs were subdivided into six classes depending on the GC content of their gene (from <40 to >60%). The boxplots represent the distribution of their respective fold‐changes after PAT1B (in orange, (Vindry et al. )) or DDX6 (in green, (Hubstenberger et al. )) silencing. The boxes represent the 25–75 percentiles and the whiskers the 10–90 percentiles. rS is the Spearman correlation coefficient. (c) Same as (a) with TOP (left panel) and histone (right panel) mRNAs in red (Courel et al. )
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Cellular distribution of human Pat1b in granules. Schematic cartoon indicating subcellular localization of GFP‐Pat1b and GFP‐Pat1b‐NES* (with inactivated NES) in cytoplasmic P‐bodies and nuclear Cajal bodies, splicing speckles and PML bodies in HeLa cells
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Domain architecture and binding partners of yeast and human Pat1 proteins. Structures of portions of N‐ter and C‐ter domains of yeast Pat1p with Dhh1 (PDB 4brw; (Sharif et al., )), Lsm1‐7 (PDB 4C8Q; (Sharif & Conti, )) and Dcp2 (PDB 5LM5; (Charenton et al., )) are shown
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Browse by Topic

Translation > Translation Regulation
RNA Processing > Splicing Regulation/Alternative Splicing
RNA Turnover and Surveillance > Regulation of RNA Stability

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