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短寿命长链非编码RNA作为化学暴露的替代指标,且LINC00152和MALAT1调节其邻近基因。

Short-lived long non-coding RNAs as surrogate indicators for chemical exposure and LINC00152 and MALAT1 modulate their neighboring genes.

作者信息

Tani Hidenori, Okuda Sayaka, Nakamura Kaoru, Aoki Motohide, Umemura Tomonari

机构信息

Environmental Management Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 16-1, Onogawa, Tsukuba, Ibaraki, Japan.

Department of Molecular Life Sciences, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, Japan.

出版信息

PLoS One. 2017 Jul 18;12(7):e0181628. doi: 10.1371/journal.pone.0181628. eCollection 2017.

Abstract

Whole transcriptome analyses have revealed a large number of novel long non-coding RNAs (lncRNAs). Although accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression, the detailed mechanisms of action of most lncRNAs remain unclear. We previously reported that a novel class of lncRNAs with a short half-life (t1/2 < 4 h) in HeLa cells, termed short-lived non-coding transcripts (SLiTs), are closely associated with physiological and pathological functions. In this study, we focused on 26 SLiTs and nuclear-enriched abundant lncRNA, MALAT1(t1/2 of 7.6 h in HeLa cells) in neural stem cells (NSCs) derived from human induced pluripotent stem cells, and identified four SLiTs (TUG1, GAS5, FAM222-AS1, and SNHG15) that were affected by the following typical chemical stresses (oxidative stress, heavy metal stress and protein synthesis stress). We also found the expression levels of LINC00152 (t1/2 of 2.1 h in NSCs), MALAT1 (t1/2 of 1.8 h in NSCs), and their neighboring genes were elevated proportionally to the chemical doses. Moreover, we confirmed that the overexpression of LINC00152 or MALAT1 upregulated the expressions of their neighboring genes even in the absence of chemical stress. These results reveal that LINC00152 and MALAT1 modulate their neighboring genes, and thus provide a deeper understanding of the functions of lncRNAs.

摘要

全转录组分析已经揭示了大量新的长链非编码RNA(lncRNA)。尽管越来越多的证据表明lncRNA在调节基因表达中发挥重要作用,但大多数lncRNA的详细作用机制仍不清楚。我们之前报道过,在HeLa细胞中一类半衰期较短(t1/2 < 4小时)的新型lncRNA,称为短寿命非编码转录本(SLiT),与生理和病理功能密切相关。在本研究中,我们聚焦于来自人类诱导多能干细胞的神经干细胞(NSC)中的26种SLiT和核富集丰富lncRNA——MALAT1(在HeLa细胞中的t1/2为7.6小时),并鉴定出4种受以下典型化学应激(氧化应激、重金属应激和蛋白质合成应激)影响的SLiT(TUG1、GAS5、FAM222 - AS1和SNHG15)。我们还发现LINC00152(在NSC中的t1/2为2.1小时)、MALAT1(在NSC中的t1/2为1.8小时)及其邻近基因的表达水平与化学剂量成比例升高。此外,我们证实即使在没有化学应激的情况下,LINC00152或MALAT1的过表达也会上调其邻近基因的表达。这些结果揭示了LINC00152和MALAT1调节其邻近基因,从而为深入了解lncRNA的功能提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b330/5515456/230937751081/pone.0181628.g001.jpg

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