MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom.
Genome Biol Evol. 2012;4(4):427-42. doi: 10.1093/gbe/evs020. Epub 2012 Mar 8.
The functional repertoire of long intergenic noncoding RNA (lincRNA) molecules has begun to be elucidated in mammals. Determining the biological relevance and potential gene regulatory mechanisms of these enigmatic molecules would be expedited in a more tractable model organism, such as Drosophila melanogaster. To this end, we defined a set of 1,119 putative lincRNA genes in D. melanogaster using modENCODE whole transcriptome (RNA-seq) data. A large majority (1.1 of 1.3 Mb; 85%) of these bases were not previously reported by modENCODE as being transcribed. Significant selective constraint on the sequences of these loci predicts that virtually all have sustained functionality across the Drosophila clade. We observe biases in lincRNA genomic locations and expression profiles that are consistent with some of these lincRNAs being involved in the regulation of neighboring protein-coding genes with developmental functions. We identify lincRNAs that may be important in the developing nervous system and in male-specific organs, such as the testes. LincRNA loci were also identified whose positions, relative to nearby protein-coding loci, are equivalent between D. melanogaster and mouse. This study predicts that the genomes of not only vertebrates, such as mammals, but also an invertebrate (fruit fly) harbor large numbers of lincRNA loci. Our findings now permit exploitation of Drosophila genetics for the investigation of lincRNA mechanisms, including lincRNAs with potential functional analogues in mammals.
长链非编码 RNA（lincRNA）分子的功能 repertoire 已开始在哺乳动物中被阐明。在更易于研究的模式生物（如黑腹果蝇 Drosophila melanogaster）中，确定这些神秘分子的生物学相关性和潜在基因调控机制将得到加速。为此，我们使用 modENCODE 全转录组（RNA-seq）数据在 D. melanogaster 中定义了一组 1,119 个推定的 lincRNA 基因。这些碱基中绝大多数（1.3 Mb 的 1.1 倍；85%）以前没有被 modENCODE 报道为转录。这些基因座序列的显著选择约束预测，实际上所有这些基因座在果蝇类群中都具有持续的功能。我们观察到 lincRNA 基因组位置和表达谱存在偏倚，这与其中一些 lincRNA 参与调节具有发育功能的邻近蛋白编码基因的假设一致。我们鉴定了可能在发育中的神经系统和雄性特异性器官（如睾丸）中起重要作用的 lincRNAs。还鉴定了 lincRNA 基因座，它们相对于附近的蛋白质编码基因座的位置在 D. melanogaster 和小鼠之间是等效的。这项研究预测，不仅脊椎动物（如哺乳动物），而且无脊椎动物（果蝇）的基因组都含有大量的 lincRNA 基因座。我们的发现现在允许利用果蝇遗传学来研究 lincRNA 机制，包括在哺乳动物中具有潜在功能类似物的 lincRNAs。
