期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 522, 期 4, 页码 945-951出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.11.191
关键词
Ankyrin repeat cluster; miRNA biogenesis; Pri-miRNA processing; Poly(ADP-ribose) polymerase; Tankyrase; Tankyrase inhibitor
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan [KAKENHI 16H06276]
- Japan Society for the Promotion of Science (JSPS) [17K07186, 19H03523]
- grants for The Nippon Foundation
- Practical Research for Innovative Cancer Control, Japan Agency for Medical Research and Development [JP19ck0106476h0001]
Tankyrases (TNKS and TNKS2) are members of poly(ADP-ribose) polymerase (PARP) family proteins. Tankyrase has multiple ankyrin repeat cluster (ARC) domains, which recognize the tankyrase-binding motifs in proteins including the telomeric protein, TRF1 and Wnt signal regulators, AXINs. However, the functional significance of tankyrase interaction with many other putative binding proteins remains unknown. Here, we found that several proteins involved in microRNA (miRNA) processing have putative tankyrase-binding motifs and their functions are regulated by tankyrase. First, chemical inhibition of tankyrase PARP activity downregulated the expression levels of precursor miRNAs (pre-miRNAs) but not primary precursor miRNAs (pri-miRNAs). A subsequent reporter assay revealed that tankyrase inhibitors or PARP-dead mutant tankyrase overexpression repress pri-miRNA processing to pre-miRNA. Conversely, a PARP-1/2 inhibitor, olaparib, did not affect pri-miRNA processing. Tankyrase ARCs bound to DGCR8 and DROSHA, which are essential components for pri-miRNA processing and have putative tankyrase-binding motifs. These observations indicate that tankyrase binds to Microprocessor, DGCR8 and DROSHA complex and modulates pri-miRNA processing to pre-miRNA. (C) 2019 Elsevier Inc. All rights reserved.
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