title: Ribosomal protein S25 dependency reveals a common mechanism for diverse internal ribosome entry sites and ribosome shunting.
abstract: During viral infection or cellular stress, cap-dependent translation is shut down. Proteins that are synthesized under these conditions use alternative mechanisms to initiate translation. This study demonstrates that at least two alternative translation initiation routes, internal ribosome entry site (IRES) initiation and ribosome shunting, rely on ribosomal protein S25 (RPS25). This suggests that they share a mechanism for initiation that is not employed by cap-dependent translation, since cap-dependent translation is not affected by the loss of RPS25. Furthermore, we demonstrate that viruses that utilize an IRES or a ribosome shunt, such as hepatitis C virus, poliovirus, or adenovirus, have impaired amplification in cells depleted of RPS25. In contrast, viral amplification of a virus that relies solely on cap-dependent translation, herpes simplex virus, is not hindered. We present a model that explains how RPS25 can be a nexus for multiple alternative translation initiation pathways.
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Marla I
authors.initials: MI
authors.lastname: Hertz
authors.forename: Dori M
authors.initials: DM
authors.lastname: Landry
authors.forename: Anne E
authors.initials: AE
authors.lastname: Willis
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Luo
authors.forename: Sunnie R
authors.initials: SR
authors.lastname: Thompson
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000257:Adenoviridae Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D011051:Poliomyelitis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D017955:Poliovirus / Q000502:physiology*; D014176:Protein Biosynthesis; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism / Q000821:virology*; D014779:Virus Replication
chemical_list: C489168:RPS25 protein, human; D012269:Ribosomal Proteins