Cellular microRNA and P bodies modulate host-HIV-1 interactions.
MicroRNAs (miRNAs), approximately 22 nt noncoding RNAs, assemble into RNA-induced silencing complexes (RISCs) and localize to cytoplasmic substructures called P bodies. Dictated by base-pair complementarity between miRNA and a target mRNA, miRNAs specifically repress posttranscriptional expression of several mRNAs. Here we report that HIV-1 mRNA interacts with RISC proteins and that disrupting P body structures enhances viral production and infectivity. In HIV-1-infected human T lymphocytes, we identified a highly abundant miRNA, miR-29a, which specifically targets the HIV-1 3'UTR region. Inhibiting miR-29a enhanced HIV-1 viral production and infectivity, whereas expressing a miR-29 mimic suppressed viral replication. We also found that specific miR-29a-HIV-1 mRNA interactions enhance viral mRNA association with RISC and P body proteins. Thus we provide an example of a single host miRNA regulating HIV-1 production and infectivity. These studies highlight the significance of miRNAs and P bodies in modulating host cell interactions with HIV-1 and possibly other viruses.
Nathans
Robin
R
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Chu
Chia-Ying
CY
Serquina
Anna Kristina
AK
Lu
Chih-Chung
CC
Cao
Hong
H
Rana
Tariq M
TM
D001483:Base Sequence; D001665:Binding Sites; D022083:Cytoplasmic Structures / Q000502:physiology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000502:physiology*; D012367:RNA, Viral / Q000737:chemistry / Q000502:physiology*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*; D043244:Ribonuclease III / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication
C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D034743:RNA-Induced Silencing Complex; C517918:DROSHA protein, human; D043244:Ribonuclease III; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases