Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits
| Autor: | Elena V. Ivanova, Audrey Berger, Katharina Strub, Elena Alkalaeva, Anne Paule Marie Scherrer |
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| Rok vydání: | 2015 |
| Předmět: |
Molecular Sequence Data
Alu element Biology Ribosome Vesicular stomatitis Indiana virus RNA polymerase III Eukaryotic translation Alu Elements Sequence Homology Nucleic Acid ddc:570 Polysome Genetics Humans Amino Acid Sequence RNA Messenger Ribosome Subunits Small Eukaryotic Messenger RNA Base Sequence Sequence Homology Amino Acid RNA Translation (biology) Molecular biology HEK293 Cells Ribonucleoproteins RNA Viral Electrophoresis Polyacrylamide Gel Ribosomes Signal Recognition Particle Protein Binding |
| Zdroj: | Nucleic Acids Research, Vol. 43, No 5 (2015) pp. 2874-2887 Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkv048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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