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PMID: 23622242 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

ADAR1 forms a complex with Dicer to promote microRNA processing and RNA-induced gene silencing.

Cell ·Vol. 153 ·No. 3 ·2013-04-25 ·Pages 575-89

Ota H, Sakurai M, Gupta R, Valente L, Wulff BE, Ariyoshi K, Iizasa H, Davuluri RV, Nishikura K

Abstract

Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs. In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction. Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms. ADAR1 differentiates its functions in RNA editing and RNAi by the formation of either ADAR1/ADAR1 homodimer or Dicer/ADAR1 heterodimer complexes, respectively. As expected, the expression of miRNAs is globally inhibited in ADAR1(-/-) mouse embryos, which, in turn, alters the expression of their target genes and might contribute to their embryonic lethal phenotype.

MeSH Terms
Adenosine Deaminase/chemistry,genetics,metabolism Animals Base Sequence DEAD-box RNA Helicases/chemistry,metabolism Dimerization Embryo, Mammalian/metabolism HEK293 Cells HeLa Cells Humans Mice MicroRNAs/metabolism Molecular Sequence Data Protein Interaction Domains and Motifs RNA Interference RNA Processing, Post-Transcriptional RNA, Small Interfering/metabolism RNA-Binding Proteins Ribonuclease III/chemistry,metabolism Up-Regulation
Chemicals
MicroRNAs RNA, Small Interfering RNA-Binding Proteins Dicer1 protein, mouse Ribonuclease III ADARB1 protein, human Adenosine Deaminase DEAD-box RNA Helicases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ota Hiromitsu
The Wistar Institute, Philadelphia, PA 19104, USA.
Sakurai Masayuki
Gupta Ravi
Valente Louis
Wulff Bjorn-Erik
Ariyoshi Kentaro
Iizasa Hisashi
Davuluri Ramana V
Nishikura Kazuko
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2013.03.024
Published
2013-04-25
Pages
575-89
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3651894
Subset
IM
Grants
NIGMS NIH HHS · GM040536 · United States
NIGMS NIH HHS · R01 GM040536 · United States
NHLBI NIH HHS · HL099342 · United States
NLM NIH HHS · R01 LM011297 · United States
NCI NIH HHS · P30 CA060553 · United States
NHLBI NIH HHS · HL070045 · United States
NHLBI NIH HHS · RC1 HL099342 · United States
NCI NIH HHS · P30 CA010815 · United States
NHLBI NIH HHS · R01 HL070045 · United States
Databases
GEO
GSE43192
External Links
PubMed source DOI: 10.1016/j.cell.2013.03.024 PMC Full Text View journal details
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