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miRNA-181 的表达可体外调节 SAMHD1 表达的特定转录后水平。

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

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.

出版信息

Biochem Biophys Res Commun. 2014 Sep 26;452(3):760-7. doi: 10.1016/j.bbrc.2014.08.151. Epub 2014 Sep 6.

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.

摘要

SAM 结构域和 HD 结构域 1(SAMHD1)是一种新发现的人类免疫缺陷病毒(HIV)-1 宿主限制因子,在 HIV-1 非允许细胞中高表达,在 HIV-1 允许细胞中低表达。SAMHD1 表达的调节机制尚不清楚。我们研究了不同细胞系中 SAMHD1 mRNA 和蛋白表达水平与 microRNA-181(miR-181)水平之间的关系。miR-181 水平与 SAMHD1 表达水平呈负相关。通过检测 miR-181 对 SAMHD1 3'非翻译区(UTR)报告荧光素酶活性以及对 SAMHD1 mRNA 和 Argonaute RISC 催化成分 2(AGO2)结合的影响,我们发现 miR-181 直接作用于 SAMHD1 3'UTR,并在转录后调节 SAMHD1 mRNA 水平。miR-181 过表达可显著降低 THP-1 细胞中 SAMHD1 的表达水平;miR-181 抑制可上调 THP-1 和 Jurkat 细胞中 SAMHD1 的表达。我们的结果表明,miR-181 通过直接结合 SAMHD1 的 3'UTR 负调控 SAMHD1 转录后水平。

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