Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury

Abstract Alternative splicing (AS) contributes to transcript and protein diversity, affecting their structure and function. However, the specific transcriptional regulatory mechanisms underlying AS in the context of hepatic ischemia reperfusion (IR) injury in mice have not been extensively character...

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Main Authors: Yongliang Hua, Xinglong Li, Bing Yin, Shounan Lu, Baolin Qian, Yongzhi Zhou, Zhongyu Li, Zhanzhi Meng, Yong Ma
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-82846-1
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author Yongliang Hua
Xinglong Li
Bing Yin
Shounan Lu
Baolin Qian
Yongzhi Zhou
Zhongyu Li
Zhanzhi Meng
Yong Ma
author_facet Yongliang Hua
Xinglong Li
Bing Yin
Shounan Lu
Baolin Qian
Yongzhi Zhou
Zhongyu Li
Zhanzhi Meng
Yong Ma
author_sort Yongliang Hua
collection DOAJ
description Abstract Alternative splicing (AS) contributes to transcript and protein diversity, affecting their structure and function. However, the specific transcriptional regulatory mechanisms underlying AS in the context of hepatic ischemia reperfusion (IR) injury in mice have not been extensively characterized. In this study, we investigated differentially alternatively spliced (DAS) genes and differentially expressed transcripts (DETs) in a mouse model of hepatic IR injury using the high throughput RNA sequencing (RNA-seq) analysis and replicate multivariate analysis of transcript splicing (rMATS) analysis. We further conducted Gene ontology (GO) term enrichment, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the protein-protein interaction (PPI) network. A total of 898 DAS genes (p ≤ 0.05) were screened out in the hepatic IR group compared to the sham group, while functional enrichment analysis revealed that DETs and DAS genes were significantly associated with the ATP-dependent chromain, splicesome and metabolic pathways. The expression level of the DAS genes: Gabpb2, Smg1, Tnrc6c, Mettl17, Smpd4, Kcnt2, D16Ertd472e, Rab3gap2, Echdc2 and Ssx2ip were verified by RT-PCR and qRT-PCR. Our findings provide a comprehensive genome-wide view of AS events in hepatic IR injury in mice, enhancing our understanding of AS dynamics and the molecular mechanisms governing alternative pre-mRNA splicing.
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spelling doaj-art-e0edeee6a31744adb5c7f3a8ff2a5bad2024-12-29T12:27:50ZengNature PortfolioScientific Reports2045-23222024-12-0114111010.1038/s41598-024-82846-1Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injuryYongliang Hua0Xinglong Li1Bing Yin2Shounan Lu3Baolin Qian4Yongzhi Zhou5Zhongyu Li6Zhanzhi Meng7Yong Ma8Department of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationDepartment of Minimally Invasive Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, the First Affiliated Hospital of Harbin Medical University, Ministry of EducationAbstract Alternative splicing (AS) contributes to transcript and protein diversity, affecting their structure and function. However, the specific transcriptional regulatory mechanisms underlying AS in the context of hepatic ischemia reperfusion (IR) injury in mice have not been extensively characterized. In this study, we investigated differentially alternatively spliced (DAS) genes and differentially expressed transcripts (DETs) in a mouse model of hepatic IR injury using the high throughput RNA sequencing (RNA-seq) analysis and replicate multivariate analysis of transcript splicing (rMATS) analysis. We further conducted Gene ontology (GO) term enrichment, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the protein-protein interaction (PPI) network. A total of 898 DAS genes (p ≤ 0.05) were screened out in the hepatic IR group compared to the sham group, while functional enrichment analysis revealed that DETs and DAS genes were significantly associated with the ATP-dependent chromain, splicesome and metabolic pathways. The expression level of the DAS genes: Gabpb2, Smg1, Tnrc6c, Mettl17, Smpd4, Kcnt2, D16Ertd472e, Rab3gap2, Echdc2 and Ssx2ip were verified by RT-PCR and qRT-PCR. Our findings provide a comprehensive genome-wide view of AS events in hepatic IR injury in mice, enhancing our understanding of AS dynamics and the molecular mechanisms governing alternative pre-mRNA splicing.https://doi.org/10.1038/s41598-024-82846-1
spellingShingle Yongliang Hua
Xinglong Li
Bing Yin
Shounan Lu
Baolin Qian
Yongzhi Zhou
Zhongyu Li
Zhanzhi Meng
Yong Ma
Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury
Scientific Reports
title Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury
title_full Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury
title_fullStr Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury
title_full_unstemmed Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury
title_short Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury
title_sort genome wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury
url https://doi.org/10.1038/s41598-024-82846-1
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