Methylmercury exposure alters RNA splicing in human neuroblastoma SK-N-SH cells: Implications from proteomic and post-transcriptional responses
Autor: | Ligang Hu, Bin He, Jiejun Gao, Yiling Li, Jianbo Shi, Qian S. Liu, Guangbo Qu, Guibin Jiang, Runzeng Liu |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Proteomics Proteome Health Toxicology and Mutagenesis RNA Splicing 010501 environmental sciences Toxicology 01 natural sciences 03 medical and health sciences Neuroblastoma Immune system Cell Line Tumor medicine Animals Humans 0105 earth and related environmental sciences Chemistry Alternative splicing Neurotoxicity RNA General Medicine Methylmercury Compounds medicine.disease Pollution Cell biology Oxidative Stress 030104 developmental biology MRNA Sequencing RNA splicing Environmental Pollutants |
Zdroj: | Environmental pollution (Barking, Essex : 1987). 238 |
ISSN: | 1873-6424 |
Popis: | 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. |
Databáze: | OpenAIRE |
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