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RNA granules: post-transcriptional and epigenetic modulators of gene expression

Abstract

The composition of cytoplasmic messenger ribonucleoproteins (mRNPs) is determined by their nuclear and cytoplasmic histories and reflects past functions and future fates. The protein components of selected mRNP complexes promote their assembly into microscopically visible cytoplasmic RNA granules, including stress granules, processing bodies and germ cell (or polar) granules. We propose that RNA granules can be both a cause and a consequence of altered mRNA translation, decay or editing. In this capacity, RNA granules serve as key modulators of post-transcriptional and epigenetic gene expression.

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Figure 1: Dynamic relationship between metazoan RNA granules.
Figure 2: Interactions between RNA granules.

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Acknowledgements

We thank T. K. Blackwell for critical reading of the manuscript and G. Seydoux for helpful suggestions. This work was supported by grants from the National Institutes of Health and the American College of Rheumatology.

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Glossary

CAR-1

(Cytokinesis, apoptosis, RNA-associated 1). An Sm-like domain-containing protein that has orthologues in mammals (RAP55), Drosophila melanogaster (TRAL) and Caenorhabditis elegans (CAR-1) RNA granules.

EDC3

(Enhancer of mRNA-decapping protein 3). A protein that is found in mammalian (EDC3) and yeast (Edc3) RNA granules.

eIF3

(Eukaryotic translation initiation factor 3). A multisubunit complex that serves as an adaptor between eIF2, eIF4G and the small ribosomal subunit, thus facilitating initiation and stabilizing the closed loop of polysomal mRNA. eIF3 is a key component of stress granules.

GW182

A large, multidomain GW repeat-containing metazoan protein that is associated with microRNAs (miRNAs) and is required for miRNA-induced gene silencing. Knockdown of GW182 inhibits the assembly of processing bodies.

PABP1

(Poly(A)-binding protein 1). A protein with orthologues in mammalian (PABP1) and Caenorhabditis elegans (PAB-1) stress granules and yeast EGP bodies (Pbp1).

PAT1

A translational repressor or enhancer of decapping orthologues that is found in mammalian (PAT1), yeast (Pat1) and Caenorhabditis elegans (PATR-1) RNA granules.

PGL-1

(P granule abnormality 1). A protein that is found in germ cell (or polar) granules that are adjacent to nuclear pores.

RCK

An RNA DEAD-box helicase that has orthologues in mammals (RCK), yeast (Dhh1), Drosophila melanogaster (ME31B) and Caenorhabditis elegans (CGH-1) RNA granules. These promote translational arrest, polysome disassembly and decapping.

TTP

(Tristetraprolin). A zinc-finger-containing protein that promotes the decay of AU-rich element (ARE)-containing mRNAs at processing bodies.

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Anderson, P., Kedersha, N. RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol 10, 430–436 (2009). https://doi.org/10.1038/nrm2694

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