Zhang Xiao-Ou, Yin Qing-Fei, Wang Hai-Bin, Zhang Yang, Chen Tian, Zheng Ping, Lu Xuhua, Chen Ling-Ling, Yang Li
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
BMC Genomics. 2014 Apr 16;15:287. doi: 10.1186/1471-2164-15-287.
Intron-derived long noncoding RNAs with snoRNA ends (sno-lncRNAs) are highly expressed from the imprinted Prader-Willi syndrome (PWS) region on human chromosome 15. However, sno-lncRNAs from other regions of the human genome or from other genomes have not yet been documented.
By exploring non-polyadenylated transcriptomes from human, rhesus and mouse, we have systematically annotated sno-lncRNAs expressed in all three species. In total, using available data from a limited set of cell lines, 19 sno-lncRNAs have been identified with tissue- and species-specific expression patterns. Although primary sequence analysis revealed that snoRNAs themselves are conserved from human to mouse, sno-lncRNAs are not. PWS region sno-lncRNAs are highly expressed in human and rhesus monkey, but are undetectable in mouse. Importantly, the absence of PWS region sno-lncRNAs in mouse suggested a possible reason why current mouse models fail to fully recapitulate pathological features of human PWS. In addition, a RPL13A region sno-lncRNA was specifically revealed in mouse embryonic stem cells, and its snoRNA ends were reported to influence lipid metabolism. Interestingly, the RPL13A region sno-lncRNA is barely detectable in human. We further demonstrated that the formation of sno-lncRNAs is often associated with alternative splicing of exons within their parent genes, and species-specific alternative splicing leads to unique expression pattern of sno-lncRNAs in different animals.
Comparative transcriptomes of non-polyadenylated RNAs among human, rhesus and mouse revealed that the expression of sno-lncRNAs is species-specific and that their processing is closely linked to alternative splicing of their parent genes. This study thus further demonstrates a complex regulatory network of coding and noncoding parts of the mammalian genome.
带有小核仁RNA末端的内含子衍生长链非编码RNA（sno-lncRNAs）在人类15号染色体上的印记普拉德-威利综合征（PWS）区域高表达。然而，来自人类基因组其他区域或其他基因组的sno-lncRNAs尚未见报道。
通过探索人类、恒河猴和小鼠的非多聚腺苷酸化转录组，我们系统地注释了在所有这三个物种中表达的sno-lncRNAs。总共，利用来自有限数量细胞系的现有数据，已鉴定出19种具有组织和物种特异性表达模式的sno-lncRNAs。虽然一级序列分析表明小核仁RNA本身从人类到小鼠是保守的，但sno-lncRNAs并非如此。PWS区域的sno-lncRNAs在人类和恒河猴中高表达，但在小鼠中无法检测到。重要的是，小鼠中缺乏PWS区域的sno-lncRNAs提示了当前小鼠模型未能完全重现人类PWS病理特征的一个可能原因。此外，在小鼠胚胎干细胞中特异性发现了一个RPL13A区域的sno-lncRNA，据报道其小核仁RNA末端会影响脂质代谢。有趣的是，RPL13A区域的sno-lncRNA在人类中几乎检测不到。我们进一步证明，sno-lncRNAs的形成通常与其母基因内的外显子可变剪接相关，物种特异性可变剪接导致sno-lncRNAs在不同动物中具有独特的表达模式。
人类、恒河猴和小鼠非多聚腺苷酸化RNA的比较转录组表明，sno-lncRNAs的表达具有物种特异性，并且它们的加工与母基因的可变剪接密切相关。因此，本研究进一步证明了哺乳动物基因组编码和非编码部分的复杂调控网络。
