Nuclear Retention of mRNA in Mammalian Tissues.
Nuclear Retention of mRNA in Mammalian Tissues.
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DOI：
10.1016/j.celrep.2015.11.036
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发表时间：
2015-12-29
期刊：
影响因子：
8.8
通讯作者：
Itzkovitz S
中科院分区：
文献类型：
--
作者：
Bahar Halpern K;Caspi I;Lemze D;Levy M;Landen S;Elinav E;Ulitsky I;Itzkovitz S
mRNA被认为主要存在于细胞质中，在那里它被翻译并最终降解。虽然mRNA的核滞留具有调节潜力，但在哺乳动物中被认为是极其罕见的。在这里，为了探索mRNA在代谢组织中的保留程度，我们将联合收割机对细胞核和细胞质RNA组分的深度测序与小鼠β细胞、肝脏和肠道中的单分子转录本成像相结合。我们确定了广泛的蛋白质编码基因的剪接的多聚腺苷酸化mRNA的水平是在细胞核中比在细胞质中更高。这些包括基因如转录因子ChREBP、Nlrp6、葡糖激酶和胰高血糖素受体。我们证明，核保留的mRNA可以有效地缓冲细胞质转录水平的噪音，来自转录爆发。我们的研究挑战了转录本主要存在于细胞质中的观点，并揭示了细胞核在抑制基因表达噪音中的作用。小鼠组织中细胞核和细胞质mRNA的全基因组目录剪接的多聚腺苷酸化mRNA保留在细胞核中用于许多蛋白质编码基因保留的基因包括ChREBP和肝脏Nlrp6，与核斑点共定位mRNA的核保留减少细胞质基因表达噪音Bahar Halpern et al.结合联合收割机全转录组和单分子方法，以证明在哺乳动物组织中，与细胞质相比，细胞核中相当一部分基因具有更高水平的剪接的多腺苷酸化mRNA。这种核保留减少了由转录爆发产生的细胞质基因表达噪音。
mRNA is thought to predominantly reside in the cytoplasm, where it is translated and eventually degraded. Although nuclear retention of mRNA has a regulatory potential, it is considered extremely rare in mammals. Here, to explore the extent of mRNA retention in metabolic tissues, we combine deep sequencing of nuclear and cytoplasmic RNA fractions with single-molecule transcript imaging in mouse beta cells, liver, and gut. We identify a wide range of protein-coding genes for which the levels of spliced polyadenylated mRNA are higher in the nucleus than in the cytoplasm. These include genes such as the transcription factor ChREBP, Nlrp6, Glucokinase, and Glucagon receptor. We demonstrate that nuclear retention of mRNA can efficiently buffer cytoplasmic transcript levels from noise that emanates from transcriptional bursts. Our study challenges the view that transcripts predominantly reside in the cytoplasm and reveals a role of the nucleus in dampening gene expression noise. Genome-wide catalog of nuclear and cytoplasmic mRNA in mouse tissues Spliced, polyadenylated mRNA is retained in the nucleus for many protein-coding genes Retained genes include ChREBP and liver Nlrp6, co-localized with nuclear speckles Nuclear retention of mRNA reduces cytoplasmic gene expression noise Bahar Halpern et al. combine whole-transcriptome and single-molecule approaches to demonstrate that a substantial fraction of genes have higher levels of spliced, polyadenylated mRNA in the nucleus compared to the cytoplasm in mammalian tissues. This nuclear retention reduces cytoplasmic gene expression noise created by transcriptional bursts.