Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways.
Adenosine deaminases acting on RNA (ADARs) are the primary factors underlying adenosine to inosine (A-to-I) editing in metazoans. Here we report the first global study of ADAR1-RNA interaction in human cells using CLIP-seq. A large number of CLIP sites are observed in Alu repeats, consistent with ADAR1's function in RNA editing. Surprisingly, thousands of other CLIP sites are located in non-Alu regions, revealing functional and biophysical targets of ADAR1 in the regulation of alternative 3' UTR usage and miRNA biogenesis. We observe that binding of ADAR1 to 3' UTRs precludes binding by other factors, causing 3' UTR lengthening. Similarly, ADAR1 interacts with DROSHA and DGCR8 in the nucleus and possibly out-competes DGCR8 in primary miRNA binding, which enhances mature miRNA expression. These functions are dependent on ADAR1's editing activity, at least for a subset of targets. Our study unfolds a broad landscape of the functional roles of ADAR1.
Department of Integrative Biology and Physiology and the Molecular Biology Institute, Los Angeles, California, 90095.
Jae Hoon
JH
Bahn
Department of Integrative Biology and Physiology and the Molecular Biology Institute, Los Angeles, California, 90095.
Jaegyoon
J
Ahn
Department of Integrative Biology and Physiology and the Molecular Biology Institute, Los Angeles, California, 90095.
Xianzhi
X
Lin
Department of Integrative Biology and Physiology and the Molecular Biology Institute, Los Angeles, California, 90095.
Qing
Q
Zhang
Department of Integrative Biology and Physiology and the Molecular Biology Institute, Los Angeles, California, 90095.
Jae-Hyung
JH
Lee
Department of Medicine University of California Los Angeles, Los Angeles, California, 90095.
Mete
M
Civelek
Department of Integrative Biology and Physiology and the Molecular Biology Institute, Los Angeles, California, 90095.
Xinshu
X
Xiao
D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D002458:Cell Fractionation; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D017423:Sequence Analysis, RNA
C474043:DGCR8 protein, human; D017931:DNA Primers; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III; C000595356:ADAR protein, human; D000243:Adenosine Deaminase