While nuclear transcription and RNA processing and localization are well established for protein coding genes (PCGs), these processes are poorly understood for lncRNAs. Here, we characterize global patterns of transcript expression, maturation and localization for mouse liver RNA, including more than 15,000 lncRNAs. PolyA-selected liver RNA was isolated and sequenced from four subcellular fractions (chromatin, nucleoplasm, total nucleus, and cytoplasm), and from the chromatin-bound fraction without polyA selection. Transcript processing, determined from normalized intronic to exonic sequence read density ratios, progressively increased for PCG transcripts in going from the chromatin-bound fraction to the nucleoplasm and then on to the cytoplasm. Transcript maturation was similar for lncRNAs in the chromatin fraction, but was significantly lower in the nucleoplasm and cytoplasm. LncRNAs were 11-fold more likely to be significantly enriched in the nucleus than cytoplasm, and 100-fold more likely to be significantly chromatin-bound than nucleoplasmic. Sequencing chromatin-bound RNA greatly increased the sensitivity for detecting lowly expressed lncRNAs and enabled us to discover and localize hundreds of novel regulated liver lncRNAs, including lncRNAs showing sex-biased expression or responsiveness to a xenobiotic agonist ligand of constitutive androstane receptor (Nr1i3). Integration of our findings with prior studies and lncRNA annotations identified candidate regulatory lncRNAs for a variety of hepatic functions based on gene co-localization within topologically associating domains or transcription divergent or antisense to PCGs associated with pathways linked to hepatic physiology and disease.

中文翻译：

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小鼠肝转录组的表达，成熟和亚细胞定位的全局分析确定了新型的性别偏见和TCPOBOP响应的长非编码RNA

虽然对于蛋白质编码基因（PCG）而言，核转录，RNA加工和定位已得到充分确立，但对于lncRNA，这些过程却知之甚少。在这里，我们表征了小鼠肝RNA的转录表达，成熟和定位的整体模式，包括超过15,000个lncRNA。从四个亚细胞级分（染色质，核质，总核和细胞质），以及未进行polyA选择的染色质结合级分中分离并测序PolyA选择的肝RNA。由标准化内含子与外显子序列读取密度之比确定的转录物处理，从染色质结合级分到核质，再到细胞质，PCG转录物逐渐增加。染色质部分中lncRNA的转录物成熟度相似，但在核质和细胞质中明显较低。与细胞质相比，LncRNAs在细胞核中显着富集的可能性高11倍，与染色质结合的细胞中，显着富集的染色质的可能性比细胞质高100倍。测序染色质结合的RNA大大提高了检测低表达的lncRNA的灵敏度，使我们能够发现并定位数百种新型肝脏调节型lncRNA，包括显示对组成型雄烷受体（Nr1i3）的异源激动剂配体表现出性别偏见或反应性的lncRNA。