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Tankyrase promotes primary precursor miRNA processing to precursor miRNA
Anna Mizutani1, Hiroyuki Seimiya1
1Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Biochemical and Biophysical Research Communications
|December 7, 2019
Summary
Tankyrases regulate microRNA (miRNA) production by binding to the Microprocessor complex. This interaction modulates the processing of primary miRNAs into precursor miRNAs, impacting miRNA biogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Gene Regulation
Background:
- Tankyrases (TNKS and TNKS2) are poly(ADP-ribose) polymerase (PARP) family proteins with ankyrin repeat cluster (ARC) domains.
- Tankyrase interactions are known with TRF1 and AXINs, but its role in other cellular processes, like microRNA (miRNA) processing, is largely unexplored.
Purpose of the Study:
- To investigate the role of tankyrases in microRNA biogenesis.
- To identify if tankyrases interact with components of the miRNA processing machinery.
Main Methods:
- Chemical inhibition of tankyrase PARP activity.
- Reporter assays to assess pri-miRNA processing.
- Overexpression of PARP-dead mutant tankyrase.
- Analysis of tankyrase ARC domain binding to DGCR8 and DROSHA.
Main Results:
- Tankyrase inhibition downregulated precursor miRNA (pre-miRNA) expression but not primary miRNA (pri-miRNA) levels.
- Tankyrase inhibition or a PARP-dead mutant repressed pri-miRNA to pre-miRNA processing.
- Olaparib, a PARP-1/2 inhibitor, did not affect pri-miRNA processing.
- Tankyrase ARCs bound to DGCR8 and DROSHA, key components of the Microprocessor complex.
Conclusions:
- Tankyrase directly binds to the Microprocessor complex, specifically DGCR8 and DROSHA.
- Tankyrase modulates the processing of pri-miRNAs into pre-miRNAs, indicating a regulatory role in miRNA biogenesis.
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