GN Ramachandran Knowledge Center for Genome Informatics, CSIR Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
Biol Direct. 2012 Aug 7;7:25. doi: 10.1186/1745-6150-7-25.
The availability of sequencing technology has enabled understanding of transcriptomes through genome-wide approaches including RNA-sequencing. Contrary to the previous assumption that large tracts of the eukaryotic genomes are not transcriptionally active, recent evidence from transcriptome sequencing approaches have revealed pervasive transcription in many genomes of higher eukaryotes. Many of these loci encode transcripts that have no obvious protein-coding potential and are designated as non-coding RNA (ncRNA). Non-coding RNAs are classified empirically as small and long non-coding RNAs based on the size of the functional RNAs. Each of these classes is further classified into functional subclasses. Although microRNAs (miRNA), one of the major subclass of ncRNAs, have been extensively studied for their roles in regulation of gene expression and involvement in a large number of patho-physiological processes, the functions of a large proportion of long non-coding RNAs (lncRNA) still remains elusive. We hypothesized that some lncRNAs could potentially be processed to small RNA and thus could have a dual regulatory output.
Integration of large-scale independent experimental datasets in public domain revealed that certain well studied lncRNAs harbor small RNA clusters. Expression analysis of the small RNA clusters in different tissue and cell types reveal that they are differentially regulated suggesting a regulated biogenesis mechanism.
Our analysis suggests existence of a potentially novel pathway for lncRNA processing into small RNAs. Expression analysis, further suggests that this pathway is regulated. We argue that this evidence supports our hypothesis, though limitations of the datasets and analysis cannot completely rule out alternate possibilities. Further in-depth experimental verification of the observation could potentially reveal a novel pathway for biogenesis.
测序技术的出现使得通过包括 RNA 测序在内的全基因组方法来理解转录组成为可能。与之前认为真核生物基因组的大部分区域没有转录活性的假设相反，最近来自转录组测序方法的证据表明，许多高等真核生物的基因组中存在广泛的转录。这些基因座中的许多编码没有明显蛋白质编码潜力的转录本，并被指定为非编码 RNA（ncRNA）。非编码 RNA 根据功能性 RNA 的大小经验上被分类为小和长非编码 RNA。这些类别中的每一个都进一步分为功能子类。尽管 microRNAs（miRNA）是非编码 RNA 的主要子类之一，因其在基因表达调控中的作用及其在大量病理生理过程中的参与而得到广泛研究，但大部分长非编码 RNA（lncRNA）的功能仍然难以捉摸。我们假设某些 lncRNA 可能会被加工成小 RNA，从而具有双重调节输出。
整合公共领域的大规模独立实验数据集表明，某些经过充分研究的 lncRNA 具有小 RNA 簇。对不同组织和细胞类型中小 RNA 簇的表达分析表明，它们是差异调节的，这表明存在一种受调控的生物发生机制。
我们的分析表明存在一种将 lncRNA 加工成小 RNA 的潜在新途径。表达分析进一步表明，这种途径是受调控的。我们认为，尽管数据集和分析的局限性不能完全排除其他可能性，但这一证据支持了我们的假设。对该观察结果进行更深入的实验验证可能会揭示一种新的生物发生途径。
