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

Abstract

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 involves 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 translation 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 mRNAs 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.

• Authors: Elena Ivanova, Audrey Berger, Anne Scherrer, Elena Alkalaeva, Katharina Strub
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 43 Issue 5 Pg. 2874-87 (Mar 11 2015) ISSN: 1362-4962 [Electronic] England
• PMID: 25697503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• RNA, Messenger
• RNA, Viral
• Ribonucleoproteins
• SRP14 protein, human
• SRP9 protein, human
• Signal Recognition Particle
• RNA

Topics

• Alu Elements (genetics)
• Amino Acid Sequence
• Base Sequence
• Electrophoresis, Polyacrylamide Gel
• HEK293 Cells
• Humans
• Molecular Sequence Data
• Protein Binding
• RNA (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA, Viral (genetics, metabolism)
• Ribonucleoproteins (genetics, metabolism)
• Ribosome Subunits, Small, Eukaryotic (genetics, metabolism)
• Ribosomes (genetics, metabolism)
• Sequence Homology, Amino Acid
• Sequence Homology, Nucleic Acid
• Signal Recognition Particle (genetics, metabolism)
• Vesicular stomatitis Indiana virus (genetics, metabolism)