title: Inhibition of translational initiation by Let-7 MicroRNA in human cells.
abstract: MicroRNAs (miRNAs) are approximately 21-nucleotide-long RNA molecules regulating gene expression in multicellular eukaryotes. In metazoa, miRNAs act by imperfectly base-pairing with the 3' untranslated region of target messenger RNAs (mRNAs) and repressing protein accumulation by an unknown mechanism. We demonstrate that endogenous let-7 microribonucleoproteins (miRNPs) or the tethering of Argonaute (Ago) proteins to reporter mRNAs in human cells inhibit translation initiation. M(7)G-cap-independent translation is not subject to repression, suggesting that miRNPs interfere with recognition of the cap. Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland.
authors.forename: Ramesh S
authors.initials: RS
authors.lastname: Pillai
authors.forename: Suvendra N
authors.initials: SN
authors.lastname: Bhattacharyya
authors.forename: Caroline G
authors.initials: CG
authors.lastname: Artus
authors.forename: Tabea
authors.initials: T
authors.lastname: Zoller
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cougot
authors.forename: Eugenia
authors.initials: E
authors.lastname: Basyuk
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Witold
authors.initials: W
authors.lastname: Filipowicz
mesh_terms: D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D010442:Peptide Chain Initiation, Translational; D010448:Peptide Initiation Factors / Q000032:analysis / Q000502:physiology; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012261:Ribonucleoproteins / Q000032:analysis / Q000502:physiology*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D035683:MicroRNAs; D010448:Peptide Initiation Factors; D012315:RNA Caps; D012333:RNA, Messenger; D012261:Ribonucleoproteins