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Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits

Publié dansNucleic acids research, vol. 43, no. 5, p. 2874-2887
Date de publication2015
Résumé

The human genome contains about 1.5 million Alu elements, which are transcribed into Alu RNAs by RNA polymerase III. Their expression is upregulated following stress and viral infection, and they associate with the SRP9/14 protein dimer in the cytoplasm forming Alu RNPs. Using cell-free translation, we have previously shown that Alu RNPs inhibit polysome formation. Here, we describe the mechanism of Alu RNP-mediated inhibition of translation initiation and demonstrate its effect on translation of cellular and viral RNAs. Both cap-dependent and IRES-mediated initiation is inhibited. Inhibition in- volves direct binding of SRP9/14 to 40S ribosomal subunits and requires Alu RNA as an assembly factor but its continuous association with 40S subunits is not required for inhibition. Binding of SRP9/14 to 40S prevents 48S complex formation by interfering with the recruitment of mRNA to 40S subunits. In cells, overexpression of Alu RNA decreases transla- tion of reporter mRNAs and this effect is alleviated with a mutation that reduces its affinity for SRP9/14. Alu RNPs also inhibit the translation of cellular mR- NAs resuming translation after stress and of viral mRNAs suggesting a role of Alu RNPs in adapting the translational output in response to stress and viral infection.

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Citation (format ISO)
IVANOVA, Elena et al. Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits. In: Nucleic acids research, 2015, vol. 43, n° 5, p. 2874–2887. doi: 10.1093/nar/gkv048
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ISSN du journal0305-1048
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Création29/04/2015 08:52:00
Première validation29/04/2015 08:52:00
Heure de mise à jour14/03/2023 23:14:23
Changement de statut14/03/2023 23:14:23
Dernière indexation16/01/2024 17:53:05
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