Podlowski Svenia, Bramlage Peter, Baumann Gert, Morano Ingo, Luther Hans Peter
Medical Clinic I, Department of Cardiology, Humboldt-University (Charité), Ziegelstr. 5-9, D10117 Berlin, Germany.
J Cell Biochem. 2002;85(1):198-207.
Natural antisense RNA is now thought to regulate, at least in part, a growing number of eukaryotic genes. It is becoming increasingly apparent that such endogenous antisense RNA molecules may modulate gene expression in a manner analogous to synthetic oligomers. Here, we report the detection of antisense-orientated RNA transcripts of cardiac specific troponin I in rat and human myocardium. Interestingly, the different sizes of the rat and human antisense cTNI transcripts suggest species-specific reverse transcription initiation sites. Moreover, for the first time in cardiomyocytes, we could demonstrate in vivo duplex formation between sense and antisense transcripts. The existence of antisense-sense duplexes represents compelling evidence and a potential mechanism for endogenous antisense transcript-mediated modulation of mRNA translation. The potential effect of attenuating translation was illustrated by in vitro and in vivo model systems. Testing several oligonucleotides based on the natural antisense sequences, the optimal region for inhibition of translation was identified as being close to the translational start codon.
现在认为天然反义RNA至少部分地调控着越来越多的真核基因。越来越明显的是，这种内源性反义RNA分子可能以类似于合成寡聚物的方式调节基因表达。在此，我们报告在大鼠和人类心肌中检测到心脏特异性肌钙蛋白I的反义方向RNA转录本。有趣的是，大鼠和人类反义cTNI转录本的不同大小表明存在物种特异性的逆转录起始位点。此外，在心肌细胞中，我们首次能够证明在体内正义和反义转录本之间形成双链体。反义-正义双链体的存在代表了令人信服的证据以及内源性反义转录本介导的mRNA翻译调节的潜在机制。体外和体内模型系统说明了减弱翻译的潜在作用。通过测试基于天然反义序列的几种寡核苷酸，确定抑制翻译的最佳区域靠近翻译起始密码子。
