Transcriptional Gene Silencing (TGS) via the RNAi Machinery in HIV-1 Infections

Biology

Gavin C Sampey²  Irene Guendel²  Ravi Das²  Elizabeth Jaworski²  Zachary Klase¹  Aarthi Narayanan²  Kylene Kehn-Hall² 

[1] Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, 9000 Rockville Pike, Bethesda, MD 20810, USA;National Center for Biodefense and Infectious Disease, School of Systems Biology, George Mason University, 10900 University Blvd, Manassas, VA 20108, USA;

关键词: HIV;    miRNA;    RNAi;    transcriptional gene silencing;    chromatin remodeler;   

DOI  :  10.3390/biology1020339

来源: mdpi

【 摘 要 】

Gene silencing via non-coding RNA, such as siRNA and miRNA, can occur at the transcriptional, post-transcriptional, and translational stages of expression. Transcriptional gene silencing (TGS) involving the RNAi machinery generally occurs through DNA methylation, as well as histone post-translational modifications, and corresponding remodeling of chromatin around the target gene into a heterochromatic state. The mechanism by which mammalian TGS occurs includes the recruitment of RNA-induced initiation of transcriptional gene silencing (RITS) complexes, DNA methyltransferases (DNMTs), and other chromatin remodelers. Additionally, virally infected cells encoding miRNAs have also been shown to manipulate the host cell RNAi machinery to induce TGS at the viral genome, thereby establishing latency. Furthermore, the introduction of exogenous siRNA and shRNA into infected cells that target integrated viral promoters can greatly suppress viral transcription via TGS. Here we examine the latest findings regarding mammalian TGS, specifically focusing on HIV-1 infected cells, and discuss future avenues of exploration in this field.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.