MicroRNA-181 expression regulates specific post-transcriptional level of SAMHD1 expression in vitro

Abstract

SAM domain and HD domain 1 (SAMHD1) is a newly discovered human immunodeficiency virus (HIV)-1 host restriction factor with high expression in HIV-1-non-permissive cells and low expression in HIV-1-permissive cells. The regulatory mechanism of SAMHD1 expression is still unclear. We examined the relationship between the expression levels of SAMHD1 mRNA and protein and microRNA-181 (miR-181) level in different cell lines. MiR-181 level was negatively correlated with SAMHD1 expression level. By examining the impact of miR-181 on SAMHD1 3' untranslated region (UTR) reporter luciferase activity and on SAMHD1 mRNA and argonaute RISC catalytic component 2 (AGO2) binding, we found that miR-181 acted directly on the SAMHD1 3' UTR and regulated SAMHD1 mRNA levels after transcription. MiR-181 over-expression significantly reduced the level of SAMHD1 expression in THP-1 cells; miR-181 inhibition up-regulated SAMHD1 expression in THP-1 and Jurkat cells. Our results suggest that miR-181 regulates the level of post-transcriptional SAMHD1 expression negatively by directly binding to the 3' UTR in SAMHD1.

Keywords: HIV-1 resistance; MiR-181; MicroRNA; Post-transcriptional regulation; SAMHD1.