Home » Key Scientific Articles » Direct binding of the Alu binding protein dimer SRP9/14 to 40S ribosomal subunits promotes stress granule formation and is regulated by Alu RNA.

Direct binding of the Alu binding protein dimer SRP9/14 to 40S ribosomal subunits promotes stress granule formation and is regulated by Alu RNA.

Significance Statement

Alu RNAs are small cytoplasmic noncoding RNAs synthesized by RNA polymerase III from Alu elements, a family of repetitive genomic sequences, which are still actively retrotransposed and are present in more than 1 million copies in primate genomes.  Under normal conditions, Alu RNA expression levels are rather low, most likely to prevent genome damage caused by frequent retrotransposition events. However, in response to stress and viral infections Alu RNA levels increase suggesting a role for these noncoding RNAs in the cellular response to stress. The studies of Ivanova et al. and Berger et al. (Nucleic Acids Res., 42, 11203–11217)
demonstrate a function for the Alu RNA in translation as well as in the formation and dissolution of stress granules. The function of the Alu RNA is mediated by the protein SRP9/14, an abundant cytoplasmic protein, which can bind to Alu RNA forming an Alu RNP. From the Alu RNP the protein can be transferred to the 40S ribosomal subunit and thereby inactivates it for translation initiation. Thus, these studies assign a role to Alu RNA in helping cells cope with stress and viral infections by adapting their translational output.

Journal Reference

Berger A1, Ivanova E1, Gareau C2, Scherrer A1, Mazroui R2, Strub K3. Nucleic Acids Res. 2014;42(17):11203-17.

1Department of Cell Biology, University of Geneva, 1211 Geneva, Switzerland.

2Département de biologie moléculaire, biochimie médicale et pathologie Université Laval, 4 Québec G1V0A6, Canada.

3Department of Cell Biology, University of Geneva, 1211 Geneva, Switzerland [email protected]

Abstract

Stress granules (SGs) are formed in response to stress, contain mRNAs, 40S ribosomal subunits, initiation factors, RNA-binding and signaling proteins, and promote cell survival. Our study describes a novel function of the protein heterodimer SRP9/14 and Alu RNA in SG formation and disassembly. In human cells, SRP9/14 exists assembled into SRP, bound to Alu RNA and as a free protein. SRP9/14, but not SRP, localizes to SGs following arsenite or hippuristanol treatment. Depletion of the protein decreases SG size and the number of SG-positive cells. Localization and function of SRP9/14 in SGs depend primarily on its ability to bind directly to the 40S subunit. Binding of SRP9/14 to 40S and Alu RNA is mutually exclusive indicating that the protein alone is bound to 40S in SGs and that  Alu RNA might competitively regulate 40S binding. Indeed, by changing the effective Alu RNA concentration in the cell or by expressing an Alu  RNA binding-defective protein we were able to influence SG formation and disassembly. Our findings suggest a model in which SRP9/14 binding  to 40S promotes SG formation whereas the increase in cytoplasmic Alu  RNA following stress promotes disassembly of SGs by disengaging  SRP9/14  from 40S.

© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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