Transcriptional regulation by miRNA mimics that target sequences downstream of gene termini.
Transcriptional regulation by miRNA mimics that target sequences downstream of gene termini.
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DOI：
10.1039/c1mb05090g
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发表时间：
2011-08
影响因子：
--
通讯作者：
Corey DR
中科院分区：
文献类型：
--
作者：
Younger ST;Corey DR
转录组研究表明，人类基因组中的蛋白质编码位点在其3′-末端与非编码RNA（ncRNA）转录物重叠。设计成与这些3′ ncRNA完全互补的小双链RNA可以调节上游基因的转录。设计RNA的强大调控表明内源性小RNA也可能识别3′ ncRNA并调节基因表达。全基因组评估显示，蛋白质编码基因的下游序列富含miRNA靶位点。我们实验测试了与人孕酮受体（PR）基因的3′-末端互补的miRNA模拟物，并观察到PR转录的抑制。这些结果表明，重叠基因末端的ncRNA转录本的识别可能是内源性小RNA的天然功能。
Transcriptome studies have revealed that protein-coding loci within the human genome are overlapped at their 3′-termini by noncoding RNA (ncRNA) transcripts. Small duplex RNAs designed to be fully complementary to these 3′ ncRNAs can modulate transcription of the upstream gene. Robust regulation by designed RNAs suggests that endogenous small RNAs might also recognize 3′ ncRNAs and regulate gene expression. A genome-wide evaluation revealed that sequences immediately downstream of protein-coding genes are enriched with miRNA target sites. We experimentally tested miRNA mimics complementary to the well-characterized 3′-terminus of the human progesterone receptor (PR) gene and observed inhibition of PR transcription. These results suggest that recognition of ncRNA transcripts that overlap gene termini may be a natural function of endogenous small RNAs.