Small RNA expression and strain specificity in the rat

Background Digital gene expression (DGE) profiling has become an established tool to study RNA expression. Here, we provide an in-depth analysis of small RNA DGE profiles from two different rat strains (BN-Lx and SHR) from six different rat tissues (spleen, liver, brain, testis, heart, kidney). We describe the expression patterns of known and novel micro (mi)RNAs and piwi-interacting (pi)RNAs. We confirmed the expression of 589 known miRNAs and identified 56 miRNAs homologous to known human or mouse miRNAs, as well as 45 new rat miRNAs. Furthermore, we confirmed specific A to I editing in brain for mir-376a/b/c and identified mir-377 as a novel editing target. In accordance with earlier findings, we observed a highly tissue-specific expression pattern for all tissues analyzed. The brain was found to express the highest number of tissue-specific miRNAs, followed by testis. Notably, our experiments also revealed robust strain-specific differential miRNA expression in the liver that is caused by genetic variation between the strains. Finally, we identified two types of germline-specific piRNAs in testis, mapping either to transposons or in strand-specific clusters. Taken together, the small RNA compendium described here advances the annotation of small RNAs in the rat genome. Strain and tissue-specific expression patterns furthermore provide a strong basis for studying the role of small RNAs in regulatory networks as well as biological process like physiology and neurobiology that are extensively studied in this model system.研究背景：数字基因表达谱（Digital Gene Expression, DGE）分析已成为研究RNA表达的成熟技术手段。本研究对两种大鼠品系（BN-Lx与SHR）的6种不同组织（脾脏、肝脏、脑组织、睾丸、心脏、肾脏）的小RNA DGE谱进行了深入剖析。我们详细描述了已知及新型微RNA（microRNA, miRNA）和piwi相互作用RNA（piwi-interacting RNA, piRNA）的表达模式：共确认589个已知miRNA的表达，鉴定出56个与人类或小鼠已知miRNA同源的miRNA，以及45个全新的大鼠特异性miRNA。此外，我们证实了mir-376a/b/c在脑组织中发生的特异性A到I编辑，并将mir-377鉴定为新型编辑靶点。与此前研究结果一致，我们观察到所有分析组织的miRNA表达均呈现高度组织特异性，其中脑组织表达的组织特异性miRNA数量最多，其次为睾丸。值得注意的是，本研究还发现两种大鼠品系的肝脏组织中存在由遗传变异导致的显著品系特异性miRNA差异表达。最后，我们在睾丸中鉴定出两类生殖系特异性piRNA，其分别定位至转座子区域或链特异性转录簇。综上，本研究描述的小RNA汇编数据集推动了大鼠基因组中小RNA的注释工作；品系与组织特异性的表达模式，更为研究小RNA在调控网络中的功能，以及该模式生物中被广泛研究的生理学、神经生物学等生物学过程提供了坚实的研究基础。