Global analysis of expression, maturation and subcellular localization of mouse liver transcriptome identifies novel sex-biased and TCPOBOP-responsive long non-coding RNAs.
Global analysis of expression, maturation and subcellular localization of mouse liver transcriptome identifies novel sex-biased and TCPOBOP-responsive long non-coding RNAs.
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小鼠肝脏转录组的表达、成熟和亚细胞定位的全局分析鉴定了新的性别偏倚和TCPOBOP响应性长非编码RNA。
DOI：
10.1186/s12864-021-07478-5
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发表时间：
2021-03-24
期刊：
影响因子：
4.4
通讯作者：
Waxman DJ
中科院分区：
文献类型：
--
作者：
Goldfarb CN;Waxman DJ
虽然蛋白质编码基因 (PCG) 的核转录、RNA 加工和定位已经很成熟，但对于长非编码 (lnc)RNA 的这些过程却知之甚少。在这里，我们描述了小鼠肝脏 RNA（包括超过 15,000 个 lncRNA）的转录表达、成熟和定位的全局模式。从四个亚细胞部分（染色质、核质、总核和细胞质）以及未经 PolyA 选择的染色质结合部分中分离出 PolyA 选择的肝脏 RNA 并进行测序。根据归一化的内含子与外显子序列读取密度比确定的转录本处理，从染色质结合部分到核质，然后到细胞质，PCG 转录本逐渐增加。染色质部分中 lncRNA 的转录成熟度相似，但核质和细胞质中的转录成熟度明显较低。 LncRNA 转录本在细胞核中显着富集的可能性比在细胞质中显着富集的可能性高 11 倍，与染色质结合的可能性比在核质中显着富集的可能性高 100 倍。对染色质结合 RNA 进行测序大大提高了检测低表达 lncRNA 的灵敏度，使我们能够发现和定位数百种新型调节性肝脏 lncRNA，包括表现出性别偏向表达或对 TCPOBOP（组成型雄甾烷受体 (Nr1i3) 的异生激动剂配体）有反应的 lncRNA。将我们的研究结果与先前的研究和lncRNA注释相结合，根据拓扑关联域内的基因共定位或与肝脏生理学和疾病相关途径相关的PCG的转录分歧或反义，确定了多种肝功能的候选调节lncRNA。在线版本包含可在 10.1186/s12864-021-07478-5 获取的补充材料。
While nuclear transcription and RNA processing and localization are well established for protein coding genes (PCGs), these processes are poorly understood for long non-coding (lnc)RNAs. 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. LncRNA transcripts 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 TCPOBOP 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. The online version contains supplementary material available at 10.1186/s12864-021-07478-5.
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影响因子：
10.5
作者：
Boutz PL;Bhutkar A;Sharp PA
通讯作者：
Sharp PA
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
4.8
作者：
Connerney, Jeannette;Lau-Corona, Dana;Waxman, David J.
通讯作者：
Waxman, David J.
影响因子：
4.8
作者：
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通讯作者：
Xie, Wen
影响因子：
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作者：
Conforto, Tara L.;Steinhardt, George F.;Waxman, David J.
通讯作者：
Waxman, David J.