A novel role for Gemin5 in mRNA translation.
In eukaryotic cells translation initiation occurs through two alternative mechanisms, a cap-dependent operating in the majority of mRNAs, and a 5'-end-independent driven by internal ribosome entry site (IRES) elements, specific for a subset of mRNAs. IRES elements recruit the translation machinery to an internal position in the mRNA through a mechanism involving the IRES structure and several trans-acting factors. Here, we identified Gemin5 protein bound to the foot-and-mouth disease virus (FMDV) and hepatitis C virus (HCV) IRES using two independent approaches, riboproteomic analysis and immunoprecipitation of photocrosslinked factors. Functional analysis performed in Gemin5 shRNA-depleted cells, or in in vitro translation reactions, revealed an unanticipated role of Gemin5 in translation control as a down-regulator of cap-dependent and IRES-driven translation initiation. Consistent with this, pull-down assays showed that Gemin5 forms part of two distinct complexes, a specific IRES-ribonucleoprotein complex and an IRES-independent protein complex containing eIF4E. Thus, beyond its role in snRNPs biogenesis, Gemin5 also functions as a modulator of translation activity.
Pacheco
Almudena
A
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco 28049 Madrid, Spain.
López de Quinto
Sonia
S
Ramajo
Jorge
J
Fernández
Noemí
N
Martínez-Salas
Encarnación
E
D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D010442:Peptide Chain Initiation, Translational; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry*; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D055532:SMN Complex Proteins / Q000378:metabolism / Q000502:physiology*
D010455:Peptides; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D055532:SMN Complex Proteins