Kaul Deepak, Ahlawat A, Gupta S Dutta
Molecular Biology Unit, Department of Experimental Medicine & Biotechnology, PGIMER, Chandigarh, 160 012, India.
Mol Cell Biochem. 2009 Mar;323(1-2):143-8. doi: 10.1007/s11010-008-9973-4. Epub 2008 Dec 11.
The recent discovery of HIV-1 genome-encoded novel microRNA (miRNA; designated as hiv1-mir-H1) having ability to target selectively and specifically human cellular AATF gene, prompted us to explore the role of this miRNA in the regulation of genes involved in cellular apoptosis, proliferation and nucleic acid-based immune mechanism governed by miRNAs. Such a study revealed that this miRNA-induced knockdown of AATF gene, within normal human blood mononuclear cells, was responsible for the suppression of genes coding for Bcl-2, c-myc, Par-4 and Dicer. Further, hiv1-mir-H1 had the capacity to downregulate expression of cellular miR149 gene recognized to target Vpr gene encoded by HIV-1. Based upon these findings, we propose an "Epigenomic Pathway" through which hiv1-mir-H1 induced AATF gene knockdown within human mononuclear cells initiates their apoptosis.
最近发现的HIV-1基因组编码的新型微小RNA（miRNA；命名为hiv1-mir-H1）具有选择性和特异性靶向人类细胞AATF基因的能力，这促使我们探索这种miRNA在调控参与细胞凋亡、增殖以及由miRNA控制的基于核酸的免疫机制的基因中的作用。这样一项研究表明，在正常人血液单核细胞中，这种miRNA诱导的AATF基因敲低导致了编码Bcl-2、c-myc、Par-4和Dicer的基因受到抑制。此外，hiv1-mir-H1能够下调细胞miR149基因的表达，已知该基因靶向HIV-1编码的Vpr基因。基于这些发现，我们提出了一条“表观基因组途径”，通过该途径，hiv1-mir-H1在人类单核细胞中诱导AATF基因敲低从而引发细胞凋亡。
