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Non-Coding RNA 2016, 2(4), 12;

TWEAK Negatively Regulates Human Dicer

CHUQ Research Center/CHUL, 2705 Blvd Laurier, Quebec, QC G1V 4G2, Canada
Department of Microbiology-Infectious Disease and Immunity and Faculty of Medicine, Université Laval, Quebec, QC G1V 0A6, Canada
The first two authors should be regarded as joint First Authors.
Author to whom correspondence should be addressed.
Academic Editor: George A. Calin
Received: 7 September 2016 / Revised: 7 October 2016 / Accepted: 14 October 2016 / Published: 25 October 2016
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The ribonuclease Dicer plays a central role in the microRNA pathway by processing microRNA precursors (pre-microRNAs) into microRNAs, a class of 19- to 24-nucleotide non-coding RNAs that regulate expression of ≈60% of the genes in humans. To gain further insights into the function and regulation of Dicer in human cells, we performed a yeast two-hybrid (Y2HB) screen using human Dicer double-stranded RNA-binding domain (dsRBD) as bait. This approach identified tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as a Dicer-interacting protein candidate. Confocal immunofluorescence microscopy revealed the colocalization of Dicer and TWEAK proteins at the perinuclear region of HeLa cells. The Dicer-TWEAK protein interaction was confirmed by coimmunoprecipitation and found not likely to be mediated by RNA. TWEAK dose-dependently reduced pre-microRNA conversion into mature microRNA in Dicer activity assays using extracts of transfected human HEK 293 cells. TWEAK expression also impaired microRNA-guided RNA silencing of a reporter gene induced by a pre-microRNA. These findings suggest a role for TWEAK—a pro-inflammatory cytokine—in regulating Dicer function and microRNA biogenesis, and its possible involvement in regulating gene expression during inflammatory processes and diseases. View Full-Text
Keywords: yeast two-hybrid system; Dicer; TWEAK; protein interaction; microRNA yeast two-hybrid system; Dicer; TWEAK; protein interaction; microRNA

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Lambert, M.; Pépin, G.; Peralta-Zaragoza, O.; Matusiak, R.; Ly, S.; Landry, P.; Provost, P. TWEAK Negatively Regulates Human Dicer. Non-Coding RNA 2016, 2, 12.

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