Ludwig Linda B
Retrovirology. 2008 Sep 11;5:79. doi: 10.1186/1742-4690-5-79.
A novel intrinsic HIV-1 antisense gene was previously described with RNA initiating from the region of an HIV-1 antisense initiator promoter element (HIVaINR). The antisense RNA is exactly complementary to HIV-1 sense RNA and capable of forming approximately 400 base-pair (bp) duplex RNA in the region of the long terminal repeat (LTR) spanning the beginning portion of TAR in the repeat (R) region and extending through the U3 region. Duplex or double-stranded RNA of several hundred nucleotides in length is a key initiating element of RNA interference (RNAi) in several species. This HIVaINR antisense RNA is also capable of forming multiple stem-loop or hairpin-like secondary structures by M-fold analysis, with at least one that perfectly fits the criteria for a microRNA (miRNA) precursor. MicroRNAs (miRNAs) interact in a sequence-specific manner with target messenger RNAs (mRNAs) to induce either cleavage of the message or impede translation. Human mRNA targets of the predicted HIVaINR antisense RNA (HAA) microRNAs include mRNA for the human interleukin-2 receptor gamma chain (IL-2RG), also called the common gamma (gammac) receptor chain, because it is an integral part of 6 receptors mediating interleukin signalling (IL-2R, IL-4R, IL-7R, IL-9R, IL-15R and IL-21R). Other potential human mRNA targets include interleukin-15 (IL-15) mRNA, the fragile x mental retardation protein (FMRP) mRNA, and the IL-1 receptor-associated kinase 1 (IRAK1) mRNA, amongst others. Thus the proposed intrinsic HIVaINR antisense RNA microRNAs (HAAmiRNAs) of the human immunodeficiency virus form complementary targets with mRNAs of a key human gene in adaptive immunity, the IL-2Rgammac, in which genetic defects are known to cause an X-linked severe combined immunodeficiency syndrome (X-SCID), as well as mRNAs of genes important in innate immunity. A new model of intrinsic RNA silencing induced by the HIVaINR antisense RNA in the absence of Tat is proposed, with elements suggestive of both small interfering RNA (siRNA) and miRNA.
先前曾描述过一种新型的HIV-1内源性反义基因，其RNA起始于HIV-1反义起始子启动子元件（HIVaINR）区域。该反义RNA与HIV-1正义RNA完全互补，并且能够在长末端重复序列（LTR）区域形成约400个碱基对（bp）的双链RNA，该区域跨越重复序列（R）区域中TAR的起始部分并延伸至U3区域。数百个核苷酸长度的双链或双链RNA是几种物种中RNA干扰（RNAi）的关键起始元件。通过M-fold分析，这种HIVaINR反义RNA也能够形成多个茎环或发夹样二级结构，其中至少有一个完全符合微小RNA（miRNA）前体的标准。微小RNA（miRNA）以序列特异性方式与靶信使RNA（mRNA）相互作用，以诱导信使RNA的切割或阻碍翻译。预测的HIVaINR反义RNA（HAA）微小RNA的人类mRNA靶标包括人类白细胞介素-2受体γ链（IL-2RG）的mRNA，也称为共同γ（γc）受体链，因为它是介导白细胞介素信号传导的6种受体（IL-2R、IL-4R、IL-7R、IL-9R、IL-15R和IL-21R）的组成部分。其他潜在的人类mRNA靶标包括白细胞介素-15（IL-15）mRNA、脆性X智力低下蛋白（FMRP）mRNA和白细胞介素-1受体相关激酶1（IRAK1）mRNA等。因此，人类免疫缺陷病毒提出的内源性HIVaINR反义RNA微小RNA（HAAmiRNAs）与适应性免疫中关键人类基因IL-2Rγc的mRNA形成互补靶标，已知该基因的遗传缺陷会导致X连锁严重联合免疫缺陷综合征（X-SCID），以及先天免疫中重要基因的mRNA。提出了一种在没有Tat的情况下由HIVaINR反义RNA诱导的内源性RNA沉默新模型，其元件暗示了小干扰RNA（siRNA）和miRNA。
