TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing.
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.
Haase
Astrid D
AD
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4508 Basel, Switzerland.
Jaskiewicz
Lukasz
L
Zhang
Haidi
H
Lainé
Sébastien
S
Sack
Ragna
R
Gatignol
Anne
A
Filipowicz
Witold
W
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
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