Transcriptional Silencing by Hairpin RNAs Complementary to a Gene Promoter
Transcriptional Silencing by Hairpin RNAs Complementary to a Gene Promoter
复制标题
DOI：
10.1089/nat.2012.0360
复制
发表时间：
2012-06-01
影响因子：
4
通讯作者：
Corey, David R.
中科院分区：
文献类型：
--
作者：
Chu, Yongjun;Kalantari, Roya;Corey, David R.
双链RNA可以靶向基因启动子并抑制转录。到目前为止，大多数研究都集中在合成RNA双链上。发夹RNA的转录沉默将有助于更好地理解内源RNA介导的细胞内转录调控。在这里，我们研究了发夹RNA对孕激素受体(PR)表达的转录沉默。我们确定引导链是PR启动子上反义转录的互补链，发夹RNA是活跃的转录沉默因子。发夹环的序列影响活性，当环具有与反义转录靶的完全互补的潜力时，获得的活性最高。引入相对于靶转录本的中心错配碱基并不能防止转录沉默，除非在引导链和乘客链上都存在错配。这些数据表明，发夹RNA可以导致转录沉默，并为靶向基因启动子的RNA调节基因的机制提供了见解。
Double-stranded RNAs can target gene promoters and inhibit transcription. To date, most research has focused on synthetic RNA duplexes. Transcriptional silencing by hairpin RNAs would facilitate a better understanding of endogenous RNA-mediated regulation of transcription within cells. Here we examine transcriptional silencing of progesterone receptor (PR) expression by hairpin RNAs. We identify the guide strand as the strand complementary to an antisense transcript at the PR promoter and that hairpin RNAs are active transcriptional silencing agents. The sequence of the hairpin loop affects activity, with the highest activity achieved when the loop has the potential for full complementarity to the antisense transcript target. Introduction of centrally mismatched bases relative to the target transcript does not prevent transcriptional silencing unless the mismatches are present on both the guide and passenger strands. These data demonstrate that hairpin RNAs can cause transcriptional silencing and offer insights into the mechanism of gene modulation by RNAs that target gene promoters.