Article
Biochemistry & Molecular Biology
Zakaria Louadi, Kevin Yuan, Alexander Gress, Olga Tsoy, Olga Kalinina, Jan Baumbach, Tim Kacprowski, Markus List
Summary: Alternative splicing plays a crucial role in regulating the functional diversity of the proteome, but its isoform-specific effects on protein-protein interactions are often overlooked. By integrating various interaction information, researchers have developed a user-friendly database called DIGGER to study mechanistic consequences of alternative splicing, providing a valuable resource for exploring the functional role of individual exons on a network level.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemical Research Methods
Jiashu Liu, Cui-Xiang Lin, Xiaoqi Zhang, Zongxuan Li, Wenkui Huang, Jin Liu, Yuanfang Guan, Hong-Dong Li
Summary: Alternative splicing (AS), a key pathway for transcriptional regulation, has been shown to be associated with complex diseases. Computational approaches for detecting disease-associated AS events have been developed. This review discusses the metrics used for characterizing AS events quantitatively. It also reviews and discusses three types of methods for detecting disease-associated splicing events: differential splicing analysis, aberrant splicing detection, and splicing-related network analysis. Additionally, methods for detecting genetic variants that potentially regulate splicing are described. Experimental comparisons are conducted to illustrate the performance of each method. The limitations of these methods are discussed, as well as potential ways to address them. This review aims to provide a systematic understanding of computational approaches for analyzing disease-associated splicing.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Sandhya Malla, Devi Prasad Bhattarai, Paula Groza, Dario Melguizo-Sanchis, Ionut Atanasoai, Carlos Martinez-Gamero, Angel-Carlos Roman, Dandan Zhu, Dung-Fang Lee, Claudia Kutter, Francesca Aguilo
Summary: This study reveals the role of ZFP207 in mouse embryonic stem cells through multiple functional analyses. Unlike human ESCs, mouse ZFP207 mainly exerts its effects by controlling AS networks and acting as RNA-binding proteins (RBPs) to maintain ESC identity and regulate neural fate commitment.
Article
Plant Sciences
Junyan Zhu, Xiaomei Yan, Shengrui Liu, Xiaobo Xia, Yanlin An, Qingshan Xu, Shiqi Zhao, Lu Liu, Rui Guo, Zhaoliang Zhang, De-Yu Xie, Chaoling Wei
Summary: By integrating metabolomics and transcriptomics, this study reveals that alternative splicing variants of the CsJAZ1 gene coordinately regulate the biosynthesis of flavan-3-ols in the tea plant, providing a better understanding of the JA-mediated flavan-3-ol biosynthesis.
Article
Oncology
Ping Ye, Yan Yang, Liqiang Zhang, Guixi Zheng
Summary: This study identified 2,212 AS events significantly associated with overall survival in esophageal carcinoma patients from TCGA database. Prognostic signatures based on these AS events were established through multivariate analysis, with risk score proving to be an independent survival factor. The interaction network between AS events and splicing factors revealed hub genes and AS events warranting further investigation, providing novel insights into tumorigenesis and progression mechanisms of esophageal carcinoma.
FRONTIERS IN ONCOLOGY
(2021)
Review
Plant Sciences
Ewa Sybilska, Agata Daszkowska-Golec
Summary: Seed germination is a vital process in a plant's life that is regulated by various mechanisms and external factors. Alternative splicing (AS) plays a significant role in abscisic acid (ABA) signaling and gene expression control. This review discusses the current understanding of AS regulators and ABA-related changes in AS during seed germination, as well as the impact of these changes on protein functionality. The advances in sequencing technology provide better tools for studying the role of AS in gene regulation.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Tassa Saldi, Kent Riemondy, Benjamin Erickson, David L. Bentley
Summary: The co-transcriptional folding of RNA plays a crucial role in splicing, A-I editing, and transcription speed. Slow transcription can lead to significant structural changes in RNA, affecting splicing and editing processes. More structured introns near the 30 splice site are excised more efficiently during co-transcriptional processing.
Article
Biochemistry & Molecular Biology
Chu-Yi Zhang, Xiao Xiao, Zhuohua Zhang, Zhonghua Hu, Ming Li
Summary: Transcriptomic and long-read sequencing analyses have revealed alternative splicing characteristics of schizophrenia risk genes, identifying new spliced isoforms and providing examples for investigating these isoforms in vitro and in vivo.
MOLECULAR PSYCHIATRY
(2022)
Review
Agriculture, Multidisciplinary
Ji-Qin Xie, Xiang Zhou, Zi-Chang Jia, Chang-Feng Su, Youjun Zhang, Alisdair R. Fernie, Jianhua Zhang, Zhi-Yan Du, Mo-Xian Chen
Summary: Disease poses a significant challenge to sustainable agricultural development. Understanding the mechanisms of host-bacteria interactions, particularly in relation to alternative splicing, is crucial for managing bacterial diseases in agriculture. This review summarizes the changes observed in alternative splicing during host-bacteria interactions and offers guidelines for plant disease management.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Plant Sciences
Shuai Lu, Cong Gao, Yongzhou Wang, Yingying He, Junrong Du, Moxian Chen, Hua Zhao, Hui Fang, Baohua Wang, Yunying Cao
Summary: This study identified U2AF65A in plant species, conducted phylogenetic and bioinformatic analyses, and studied the localization and stress responses of OsU2AF65A in rice. Using Arabidopsis and rice mutants, the importance of U2AF65A in plant growth and stress responses was demonstrated. These findings provide an overview of the U2AF65 gene family and its role in plant development and stress tolerance.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemical Research Methods
Delong Zhou, Yvan Tran, Sherif Abou Elela, Michelle S. Scott
Summary: SAPFIR is a predictor of protein features associated with alternative splicing events, allowing for rapid identification of functional alternative splicing events and analysis of proteins generated from diverse genes, providing guidance on the impact on cellular functions.
BMC BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Naima Ahmed Fahmi, Heba Nassereddeen, Jaewoong Chang, Meeyeon Park, Hsinsung Yeh, Jiao Sun, Deliang Fan, Jeongsik Yong, Wei Zhang
Summary: AS-Quant is a robust program for identifying alternative splicing events from RNA-seq data. It outperforms other widely used tools by calculating read coverage, categorizing event types, and generating short read coverage plots. The significant alternative splicing events identified by AS-Quant were validated using RT-PCR experiments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Weidi Wang, Yucan Chen, Jingjing Zhao, Liang Chen, Weichen Song, Li Li, Guan Ning Lin
Summary: The study explored the protein-protein interaction of NSD2 and its role in WHS and myeloma. Through immunoprecipitation mass spectrometry analysis, 890 isoform-specific PPI partners were identified, further divided into four categories of exon-specific interactome. The research revealed the diverse roles of NSD2 in RNA splicing processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Shuting Lin, Soojin Yi, Peng Qiu
Summary: The relationship between DNA methylation and alternative splicing was examined in this study using multiple omics data types from TCGA. The study revealed significant associations between CpG sites and exon expression, consistent across different cancer contexts. CpG sites correlated with exon expression were also found to be more likely to be associated with patient survival outcomes. Furthermore, CpG sites were shown to have a stronger correlation with exon expression than with the expression of isoforms harboring the corresponding exons.
Article
Cell Biology
Wenrui Qu, Hongjuan Jin, Bing-Peng Chen, Jun Liu, Rui Li, Wenlai Guo, Heng Tian
Summary: The study reveals that CPEB3 is a critical regulator of alternative splicing in neurogenesis, with the ability to partially modulate gene splicing related to neural development, neuron cycle, neurotrophin, synapse, and specific development pathways.
Article
Biochemistry & Molecular Biology
David Talavera, Simon C. Lovell, Simon Whelan
MOLECULAR BIOLOGY AND EVOLUTION
(2015)
Article
Multidisciplinary Sciences
Christopher J. Kershaw, Joseph L. Costello, David Talavera, William Rowe, Lydia M. Castelli, Paul F. G. Sims, Christopher M. Grant, Mark P. Ashe, Simon J. Hubbard, Graham D. Pavitt
SCIENTIFIC REPORTS
(2015)
Article
Evolutionary Biology
Ryan M. Ames, David Talavera, Simon G. Williams, David L. Robertson, Simon C. Lovell
BMC EVOLUTIONARY BIOLOGY
(2016)
Article
Computer Science, Artificial Intelligence
Mario Garza-Fabre, Shaun M. Kandathil, Julia Handl, Joshua Knowles, Simon C. Lovell
EVOLUTIONARY COMPUTATION
(2016)
Article
Genetics & Heredity
Panagiotis I. Sergouniotis, Stephanie J. Barton, Sarah Waller, Rahat Perveen, Jamie M. Ellingford, Christopher Campbell, Georgina Hall, Rachel L. Gillespie, Sanjeev S. Bhaskar, Simon C. Ramsden, Graeme C. Black, Simon C. Lovell
ORPHANET JOURNAL OF RARE DISEASES
(2016)
Article
Biochemistry & Molecular Biology
Shaun M. Kandathil, Julia Handl, Simon C. Lovell
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2016)
Article
Biology
Samina Naseeb, Ryan M. Ames, Daniela Delneri, Simon C. Lovell
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2017)
Article
Multidisciplinary Sciences
David Talavera, Christopher J. Kershaw, Joseph L. Costello, Lydia M. Castelli, William Rowe, Paul F. G. Sims, Mark P. Ashe, Chris M. Grant, Graham D. Pavitt, Simon J. Hubbard
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Xiaoguang Xu, James M. Eales, Artur Akbarov, Hui Guo, Lorenz Becker, David Talavera, Fehzan Ashraf, Jabran Nawaz, Sanjeev Pramanik, John Bowes, Xiao Jiang, John Dormer, Matthew Denniff, Andrzej Antczak, Monika Szulinska, Ingrid Wise, Priscilla R. Prestes, Maciej Glyda, Pawel Bogdanski, Ewa Zukowska-Szczechowska, Carlo Berzuini, Adrian S. Woolf, Nilesh J. Samani, Fadi J. Charchar, Maciej Tomaszewski
NATURE COMMUNICATIONS
(2018)
Article
Genetics & Heredity
James M. Eales, Xiao Jiang, Xiaoguang Xu, Sushant Saluja, Artur Akbarov, Eddie Cano-Gamez, Michelle T. McNulty, Christopher Finan, Hui Guo, Wojciech Wystrychowski, Monika Szulinska, Huw B. Thomas, Sanjeev Pramanik, Sandesh Chopade, Priscilla R. Prestes, Ingrid Wise, Evangelos Evangelou, Mahan Salehi, Yusif Shakanti, Mikael Ekholm, Matthew Denniff, Alicja Nazgiewicz, Felix Eichinger, Bradley Godfrey, Andrzej Antczak, Maciej Glyda, Robert Krol, Stephen Eyre, Jason Brown, Carlo Berzuini, John Bowes, Mark Caulfield, Ewa Zukowska-Szczechowska, Joanna Zywiec, Pawel Bogdanski, Matthias Kretzler, Adrian S. Woolf, David Talavera, Bernard Keavney, Pasquale Maffia, Tomasz J. Guzik, Raymond T. O'Keefe, Gosia Trynka, Nilesh J. Samani, Aroon Hingorani, Matthew G. Sampson, Andrew P. Morris, Fadi J. Charchar, Maciej Tomaszewski
Summary: Analyzing genotype, gene expression, alternative splicing, and DNA methylation profiles of human kidney samples can provide insights into the effects of common variants influencing blood pressure. Mendelian randomization revealed the effects of blood pressure on renal outcomes.
Article
Genetics & Heredity
Alexandru Chelu, Simon G. Williams, Bernard D. Keavney, David Talavera
Summary: Although several genes involved in the development of Tetralogy of Fallot have been identified, a genetic diagnosis is still unavailable for the majority of patients. In this study, we conducted a joint analysis of functionally related genes and identified 12 gene groups that significantly contribute to the burden of Tetralogy of Fallot. Further analysis revealed that genes with high-impact variants tend to interact with each other. These findings suggest that studying the protein interaction network of known causative genes may lead to the discovery of additional candidate genes. Additionally, our results demonstrate that the joint analysis of functionally related genes can be a useful complement to traditional single-gene analyses.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Multidisciplinary Sciences
Dominic J. F. Byrne, Simon G. Williams, Apostol Nakev, Simon Frain, Stephanie L. Baross, Jorgen Vestbo, Bernard D. Keavney, David Talavera
Summary: Adults with congenital heart disease (CHD) face an increased risk of developing chronic obstructive pulmonary disease (COPD). A case-control analysis involving 3385 CHD cases and 479,765 healthy controls showed a substantially greater risk of COPD in CHD patients compared to healthy controls. The association remained robust even after adjusting for smoking and other factors known to affect COPD risk. Care for adults with CHD should focus on mitigating the risk of COPD, possibly through increased smoking cessation support.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Martin D. Jennings, Priya Srivastava, Christopher J. Kershaw, David Talavera, Christopher M. Grant, Graham D. Pavitt
Summary: Cells respond to oxidative stress by reprogramming gene expression to enhance levels of antioxidant enzymes. In Saccharomyces cerevisiae, proteins Slf1 and Sro9 play a role in protein synthesis adaptation during stress. Slf1 is identified as a ribosome-associated translational modulator that promotes translation of highly-translated mRNAs, facilitating cell survival and adaptation to stress.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Joseph L. Costello, Christopher J. Kershaw, Lydia M. Castelli, David Talavera, William Rowe, Paul F. G. Sims, Mark P. Ashe, Christopher M. Grant, Simon J. Hubbard, Graham D. Pavitt
