MicroRNA 4651 regulates nonsense-mediated mRNA decay by targeting SMG9 mRNA.

Nonsense-mediated mRNA decay (NMD) is originally identified as a conserved RNA surveillance mechanism that rapidly degrades aberrant mRNA containing premature termination codons (PTCs). However, the molecular regulation mechanisms by which microRNAs inhibit NMD has not been well understood. Here we identified that miR-4651 participated in the NMD pathway by downregulating expression levels of SMG9. We provided evidences that (1) Overexpression of miR-4651 mimic significantly inhibited the expression of SMG9 (P < 0.05); (2) NMD substrates genes, TBL2 and GADD45B were both increased at mRNA and protein expression levels when SMG9 was suppressed by siRNA, whereas decreased by SMG9 overexpression; (3) Expression of SMG9 was significantly increased but TBL2, GADD45B were significantly decreased when cells transfected with miR-4651 inhibitor (P < 0.05). These results indicated that miR-4651 regulated NMD by targeting SMG9 mRNA. Our study highlights that miR-4651 represses NMD. miR-4651 targets SMG9 and represses the expression levels of SMG9. NMD activity is decreased additionally when SMG9 is inhibited. The present study provides evidence for microRNA/NMD regulatory mechanism.