title: 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.affiliation: Département de biologie cellulaire, Université de Genève, Sciences III, 1211 Genève, Switzerland Katharina.Strub@unige.ch.
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.affiliation: Département de biologie cellulaire, Université de Genève, Sciences III, 1211 Genève, Switzerland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Berger
authors.affiliation: Département de biologie cellulaire, Université de Genève, Sciences III, 1211 Genève, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Scherrer
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Alkalaeva
authors.affiliation: Département de biologie cellulaire, Université de Genève, Sciences III, 1211 Genève, Switzerland Katharina.Strub@unige.ch.
authors.forename: Katharina
authors.initials: K
authors.lastname: Strub
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D054682:Ribosome Subunits, Small, Eukaryotic / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D018271:Signal Recognition Particle / Q000235:genetics / Q000378:metabolism*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D012261:Ribonucleoproteins; C490326:SRP14 protein, human; C486350:SRP9 protein, human; D018271:Signal Recognition Particle; D012313:RNA