Younger Scott T, Corey David R
Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.
Mol Biosyst. 2011 Aug;7(8):2383-8. doi: 10.1039/c1mb05090g. Epub 2011 May 18.
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.
转录组研究表明,人类基因组中的蛋白质编码基因座在其3'末端与非编码RNA(ncRNA)转录本重叠。设计为与这些3' ncRNA完全互补的小双链RNA可以调节上游基因的转录。设计的RNA的强大调控作用表明,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,蛋白质编码基因紧邻下游的序列富含miRNA靶位点。我们通过实验测试了与人类孕激素受体(PR)基因特征明确的3'末端互补的miRNA模拟物,并观察到PR转录受到抑制。这些结果表明,识别与基因末端重叠的ncRNA转录本可能是内源性小RNA的一种天然功能。