title: TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing.
abstract: Dicer is a key enzyme involved in RNA interference (RNAi) and microRNA (miRNA) pathways. It is required for biogenesis of miRNAs and small interfering RNAs (siRNAs), and also has a role in the effector steps of RNA silencing. Apart from Argonautes, no proteins are known to associate with Dicer in mammalian cells. In this work, we describe the identification of TRBP (human immunodeficiency virus (HIV-1) transactivating response (TAR) RNA-binding protein) as a protein partner of human Dicer. We show that TRBP is required for optimal RNA silencing mediated by siRNAs and endogenous miRNAs, and that it facilitates cleavage of pre-miRNA in vitro. TRBP had previously been assigned several functions, including inhibition of the interferon-induced double-stranded RNA-regulated protein kinase PKR and modulation of HIV-1 gene expression by association with TAR. The TRBP-Dicer interaction shown raises interesting questions about the potential interplay between RNAi and interferon-PKR pathways.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4508 Basel, Switzerland.
authors.forename: Astrid D
authors.initials: AD
authors.lastname: Haase
authors.forename: Lukasz
authors.initials: L
authors.lastname: Jaskiewicz
authors.forename: Haidi
authors.initials: H
authors.lastname: Zhang
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lainé
authors.forename: Ragna
authors.initials: R
authors.lastname: Sack
authors.forename: Anne
authors.initials: A
authors.lastname: Gatignol
authors.forename: Witold
authors.initials: W
authors.lastname: Filipowicz
mesh_terms: D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D005809:Genes, Regulator; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D007372:Interferons; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D019892:eIF-2 Kinase / Q000235:genetics*; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D007372:Interferons; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D043244:Ribonuclease III; D015534:Trans-Activators; D019892:eIF-2 Kinase; D000099253:Trans-Activation Responsive RNA-Binding Protein