Methylmercury exposure alters RNA splicing in human neuroblastoma SK-N-SH cells: Implications from proteomic and post-transcriptional

被引：11

作者：

Li, Yiling ^{[1
,2
]}

He, Bin ^{[1
,2
]}

Gao, Jiejun ^{[1
,2
]}

Liu, Qian S. ^{[1
,2
]}

Liu, Runzeng ^{[1
,2
]}

Qu, Guangbo ^{[1
,2
]}

Shi, Jianbo ^{[1
,2
]}

Hu, Ligang ^{[1
,3
]}

Jiang, Guibin ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100190, Peoples R China

[3] Jianghan Univ, Inst Environm & Hlth, Wuhan 430056, Hubei, Peoples R China

来源：

ENVIRONMENTAL POLLUTION | 2018年 / 238卷

基金：

中国国家自然科学基金;

关键词：

Methylmercury; Mercury chloride; Differentially expressed proteins; Alternative splicing; SK-N-SH cells; PRE-MESSENGER-RNA; MERCURY TOXICITY; OXIDATIVE STRESS; METHYL MERCURY; NEUROTOXICITY; PROTEINS; BRAIN; HNRNP; GENE; ETHYLMERCURY;

D O I：

10.1016/j.envpol.2018.03.019

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

The neurotoxic effects of methylmercury (MeHg) have been intensively studied. However, the molecular mechanisms responsible for the neurotoxicity of MeHg are not fully understood. To decipher these mechanisms, proteomic and high-throughput mRNA sequencing (RNA-seq) technique were utilized, comprehensively evaluating the cellular responses of human neuroblastoma SK-N-SH cells to MeHg exposure. Proteomic results revealed that MeHg exposure interfered with RNA splicing via splicesome, along with the known molecular mechanisms of mercury-related neurotoxicity (e.g. oxidative stress, protein folding, immune system processes, and cytoskeletal organization). The effects of MeHg on RNA splicing were further verified using RNA-seq. Compared to control, a total of 658 aberrant RNA alternative splicing (AS) events were observed after MeHg exposure. Proteomics and RNA-seq results also demonstrated that mercury chloride (HgCl2) influenced the expression levels of several RNA splicing related proteins and 676 AS events compared to control. These results suggested that RNA splicing could be a new molecular mechanism involved in MeHg and HgCl2 neurotoxicity. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：213 / 221

页数：9