TWEAK Negatively Regulates Human Dicer
AbstractThe 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
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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.
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(4):12.Chicago/Turabian Style
Lambert, Marine; Pépin, Geneviève; Peralta-Zaragoza, Oscar; Matusiak, Raphaël; Ly, Sophia; Landry, Patricia; Provost, Patrick. 2016. "TWEAK Negatively Regulates Human Dicer." Non-Coding RNA 2, no. 4: 12.