Natural antisense transcripts as therapeutic targets.
Natural antisense transcripts as therapeutic targets.
复制标题
DOI：
10.1016/j.ddstr.2013.03.001
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
在21世纪之交，分子生物学的核心教条受到了一个意外发现的挑战，即从人类基因组转录的所有基因中，只有1.2%实际上是编码蛋白质的。事实上，人类和小鼠基因组的大规模测序显示，其余99%由数千种非蛋白质编码转录物或“非编码rna”（ncRNA）组成，它们形成复杂和重叠的网络，并在各种细胞和组织中充当转录和转录后调节因子[1-3]。根据它们的大小，它们大致分为短（< 200bp）和长（lncRNAs）[4]。虽然短的ncrna，特别是microrna (mirna)，现在已经被广泛地表征，但直到最近，人们对大量的长非编码转录本的关注还很少，而长非编码转录本以前被许多人视为基因组垃圾或“暗物质”。然而，观察到大量的lncrna在物种间是保守的，并且以区域、时间和细胞特异性的方式表达，这表明这些转录本确实可能具有功能相关性bb0。特别是在过去的几年里，lncrna吸引了越来越多的兴趣，因为越来越多的证据表明它们在各种细胞过程中起着关键作用。2006年，有人提出lncrna，如天然反义转录物（NATs），代表了新的治疗靶点，可以影响基因或通路的表达，而这些基因或通路以前被认为是不可药物的。从那以后的几年里，我们不仅对这些RNA分子如何发挥其控制作用有了更深入的了解，而且这种创新思维也激发了新的生物技术公司的形成。在这里，我们描述了NATs的各种调节功能，以及它们与疾病的新联系，并重点关注它们作为可行治疗靶点的持续前景。
At the turn of the 21st century, the central dogma of molecular biology was challenged by the unexpected discovery that only 1.2% of all genes transcribed from the human genome actually encode proteins. In fact, large-scale sequencing of the human and mouse genomes revealed that the other 99% is comprised of thousands of non-protein coding transcripts or ‘non-coding RNAs’(ncRNA) that form complex and overlapping networks, and act as transcriptional and post-transcriptional regulators within various cells and tissues [1-3]. These are broadly classified, according to their sizes, into short (< 200bp) and long ncRNAs (lncRNAs)[4]. Although short ncRNAs, in particular microRNAs (miRNAs), have now been extensively characterized [5], until recently less attention had been paid to the abundance of long non-coding transcripts, previously viewed by many as genomic junk or ‘dark matter’. However, observations that a significant number of lncRNAs are conserved across species, and are expressed in a regional, temporal and cell-specific manner, suggested that these transcripts could indeed have functional relevance [6]. Particularly within the last few years, lncRNAs have been attracting increasing interest, in light of growing evidence that they play key roles in a variety of cellular processes. In 2006, it was proposed that lncRNAs, such as the natural antisense transcripts (NATs), represented novel therapeutic targets to influence the expression of genes or pathways that were previously considered to be undruggable [7]. In the years since, not only have we developed a greater understanding as to how these RNA molecules exert their control, but this type of innovative thinking has also inspired the formation of new biotech companies. Here we describe the various regulatory functions of NATs, as well as their emerging links to disease, and focus on their continued promise as viable therapeutic targets.