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内含子是细胞对饥饿反应的中介。

Introns are mediators of cell response to starvation.

机构信息

RNA Group, Département de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

RNA Group, Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

出版信息

Nature. 2019 Jan;565(7741):612-617. doi: 10.1038/s41586-018-0859-7. Epub 2019 Jan 16.

Abstract

Introns are ubiquitous features of all eukaryotic cells. Introns need to be removed from nascent messenger RNA through the process of splicing to produce functional proteins. Here we show that the physical presence of introns in the genome promotes cell survival under starvation conditions. A systematic deletion set of all known introns in budding yeast genes indicates that, in most cases, cells with an intron deletion are impaired when nutrients are depleted. This effect of introns on growth is not linked to the expression of the host gene, and was reproduced even when translation of the host mRNA was blocked. Transcriptomic and genetic analyses indicate that introns promote resistance to starvation by enhancing the repression of ribosomal protein genes that are downstream of the nutrient-sensing TORC1 and PKA pathways. Our results reveal functions of introns that may help to explain their evolutionary preservation in genes, and uncover regulatory mechanisms of cell adaptations to starvation.

摘要

内含子是所有真核细胞的普遍特征。通过剪接过程,内含子需要从新生信使 RNA 中去除,以产生功能性蛋白质。在这里,我们表明基因组中内含子的存在促进了细胞在饥饿条件下的存活。对芽殖酵母基因中所有已知内含子的系统缺失集表明,在大多数情况下,当营养物质耗尽时,带有内含子缺失的细胞会受到损害。内含子对生长的这种影响与宿主基因的表达无关,即使宿主 mRNA 的翻译被阻断,这种影响仍然存在。转录组和遗传分析表明,内含子通过增强对营养感应 TORC1 和 PKA 途径下游核糖体蛋白基因的抑制,促进对饥饿的抵抗。我们的结果揭示了内含子的功能,这可能有助于解释它们在基因中的进化保存,并揭示了细胞适应饥饿的调节机制。

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