title: HuR and Ago2 Bind the Internal Ribosome Entry Site of Enterovirus 71 and Promote Virus Translation and Replication.
abstract: EV71 (enterovirus 71) RNA contains an internal ribosomal entry site (IRES) that directs cap-independent initiation of translation. IRES-dependent translation requires the host's translation initiation factors and IRES-associated trans-acting factors (ITAFs). We reported recently that mRNA decay factor AUF1 is a negative-acting ITAF that binds IRES stem-loop II. We also reported that the small RNA-processing enzyme Dicer produces at least four small RNAs (vsRNAs) from the EV71 IRES. One of these, vsRNA1, derived from IRES stem-loop II, reduces IRES activity and virus replication. Since its mechanism of action is unknown, we hypothesized that it might control association of ITAFs with the IRES. Here, we identified the mRNA stability factor HuR and the RISC subunit Argonaute 2 (Ago2) as two ITAFs that bind stem-loop II. In contrast to AUF1, HuR and Ago2 promote EV71 IRES activity and virus replication. In vitro RNA-binding assays revealed that vsRNA1 can alter association of Ago2, HuR, and AUF1 with stem-loop II. This presents a possible mechanism by which vsRNA1 could control viral translation and replication.
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Lin
authors.affiliation: Department of Biochemistry & Molecular Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Brewer
authors.affiliation: Department of Biochemistry & Molecular Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, United States of America.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Li
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D060565:Argonaute Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D000067780:ELAV-Like Protein 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D055785:Gene Knockdown Techniques; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism; D006801:Humans; D000067556:Internal Ribosome Entry Sites; D055029:Inverted Repeat Sequences / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D000067780:ELAV-Like Protein 1; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D000067556:Internal Ribosome Entry Sites; D012367:RNA, Viral