Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons
Anne L. Sapiro,
Emily C. Freund,
Lucas Restrepo,
Huan-Huan Qiao,
Amruta Bhate,
Qin Li,
Jian-Quan Ni,
Timothy J. Mosca,
Jin Billy Li
Affiliations
Anne L. Sapiro
Department of Genetics, Stanford University, Stanford, CA 94305, USA
Emily C. Freund
Department of Genetics, Stanford University, Stanford, CA 94305, USA
Lucas Restrepo
Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA
Huan-Huan Qiao
Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
Amruta Bhate
Department of Genetics, Stanford University, Stanford, CA 94305, USA
Qin Li
Department of Genetics, Stanford University, Stanford, CA 94305, USA
Jian-Quan Ni
Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing, China
Timothy J. Mosca
Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA
Jin Billy Li
Department of Genetics, Stanford University, Stanford, CA 94305, USA; Corresponding author
Summary: Adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but few trans regulators of ADARs are known in vivo. Here, we screen RNA-binding proteins for roles in editing regulation with knockdown experiments in the Drosophila brain. We identify zinc-finger protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular junction architecture and fly mobility. Furthermore, Zn72D’s regulatory role in RNA editing is conserved because the mammalian homolog of Zn72D, Zfr, regulates editing in mouse primary neurons. The broad and conserved regulation of ADAR editing by Zn72D in neurons sustains critically important editing events.
