Article
Biochemistry & Molecular Biology
Clarisse van der Feltz, Brandon Nikolai, Charles Schneider, Joshua C. Paulson, Xingyang Fu, Aaron A. Hoskins
Summary: Spliceosome catalysis is influenced by nonessential components, with Ecm2 playing a role in stabilizing catalytic sites and promoting alternate splice site usage. The interaction between Cwc2 and Ecm2 can fine-tune the spliceosome active site in unique ways, allowing for regulation of splicing of pre-mRNAs containing weak or alternate splice sites.
Review
Immunology
Frank Fang Yao Lee, Scott Alper
Summary: While TLR signaling is necessary to combat infection, persistent inflammation can cause damage and contribute to various inflammatory disorders. Alternative pre-mRNA splicing plays a role in terminating TLR signaling by producing dominant negative inhibitors that limit inflammation. Understanding the production and function of these alternative isoforms may provide insights into inflammatory disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sierra L. L. Love, Joseph D. D. Emerson, Kazunori Koide, Aaron A. A. Hoskins
Summary: Pre-mRNA splicing is a crucial step in human gene expression, carried out by a macromolecular machine known as the spliceosome. Mutations in this machinery can lead to various human diseases. This review provides an overview of the main features of the pre-mRNA splicing machinery in humans and how changes in its components' function can result in diseases ranging from blindness to cancers. The article also discusses drugs that interact with the spliceosome to alter splicing outcomes and speculates on future treatments for spliceosomopathies.
Review
Biochemistry & Molecular Biology
Jingya Lin, Ziqiang Zhu
Summary: This review discusses how plants adapt to high temperatures through pre-mRNA splicing, and the significance of this splicing regulation for plant growth and development.
PLANT MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yechun Hong, Yang Gao, Jia Pang, Huazhong Shi, Tingting Li, Huiying Meng, Dali Kong, Yunjuan Chen, Jian-Kang Zhu, Zhen Wang
Summary: Salt stress negatively affects crop production. Previous studies have implicated several spliceosome components in regulating salt stress responses in plants, but the molecular basis is not fully understood. This study shows that the spliceosomal core protein SmEb is essential for salt tolerance in Arabidopsis. Transcriptome analysis reveals that SmEb modulates alternative splicing of hundreds of pre-mRNAs in response to salt stress. Further investigation demonstrates the crucial role of SmEb in maintaining the proper ratio of two RCD1 splicing variants important for salt stress response. Moreover, RCD1.1, but not RCD1.2, interacts with stress regulators and attenuates salt sensitivity in the smeb-1 mutant by reducing salt-induced cell death. Overall, our findings highlight the essential role of SmEb in regulating alternative pre-mRNA splicing in salt stress response.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christophe Rachez, Rachel Legendre, Mickael Costallat, Hugo Varet, Jia Yi, Etienne Kornobis, Christian Muchardt
Summary: HP1 proteins, known for marking heterochromatin and gene silencing, are also RNA-binding proteins. HP1 gamma, in particular, is targeted to hexameric RNA motifs and SINE transposable elements, tethering unspliced pre-mRNA to chromatin through intronic regions and limiting the usage of intronic cryptic splice sites during transcription. This reveals new insights into the relationship between chromatin and co-transcriptional splicing.
Article
Multidisciplinary Sciences
Yang Pan, John W. Phillips, Beatrice D. Zhang, Miyako Noguchi, Eric Kutschera, Jami McLaughlin, Pavlo A. Nesterenko, Zhiyuan Mao, Nathanael J. Bangayan, Robert Wang, Wendy Tran, Harry T. Yang, Yuanyuan Wang, Yang Xu, Matthew B. Obusan, Donghui Cheng, Alex H. Lee, Kathryn E. Kadash-Edmondson, Ameya Champhekar, Cristina Puig-Saus, Antoni Ribas, Robert M. Prins, Christopher S. Seet, Gay M. Crooks, Owen N. Witte, Yi Xing
Summary: This study describes a computational platform called IRIS that can discover tumor antigens derived from alternative splicing, providing potential targets for TCR and CAR-T immunotherapies. Through the analysis of transcriptomics and immuno-peptidomics data, the study demonstrates that the predicted targets by IRIS can bind with HLA molecules. The study illustrates the contribution of alternative splicing to the repertoire of tumor antigens and demonstrates the utility of IRIS in discovering AS-derived antigens and expanding cancer immunotherapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Kiran Kumar Kolathur, Pallavi Sharma, Nagesh Y. Y. Kadam, Navneet Shahi, Ane Nishitha, Kavita Babu, Shravan Kumar Mishra
Summary: UBL-5 is a ubiquitin-like protein that associates with proteins non-covalently and plays a conserved pre-mRNA splicing function in Caenorhabditis elegans. UBL-5 interacts with splicing factors Snu66/SART-1 and PRP-38 and other spliceosomal proteins. UBL-5 mutants in C. elegans exhibit developmental defects and splicing abnormalities for specific targets.
Article
Cell Biology
Yanfei Wang, Cuiqiao Zhang, Wu Peng, Haibo Du, Yuehui Xi, Zhigang Xu
Summary: This study further explored the role of RBM24 in hearing and balance through conditional knockout mice and found that the loss of RBM24 results in severe deficits. It was observed that the development of hair cells was significantly affected, leading to degeneration and disorganization of the hair bundles. RNAseq analysis also identified several genes whose mRNA stability or pre-mRNA alternative splicing is affected by RBM24 knockout.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bin Guo, Xiaorui Shi, Zhe Ma, Moxuan Ji, Chu Tang, Fu Wang
Summary: A genetically engineered ratiometric dual luciferase reporter has been developed to continuously quantify changes in mRNA splice variants in vivo. This reporter system minimizes the influence of indirect factors on splicing within the same individual, with the ratio of two luciferase intensities representing the dynamic splicing efficiency of pre-mRNA. This tool offers a convenient and robust method for screening and identifying small molecules or trans-acting factors affecting specific splicing reactions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Plant Sciences
Wei Lan, Yuhao Qiu, Yun Xu, Yalin Liu, Ying Miao
Summary: Alternative splicing plays a critical role in plant development and response to environmental stress. Post-translational modification, such as protein ubiquitination, has been found to regulate the activity and stability of spliceosomal proteins, providing another layer of regulation for alternative splicing. This review summarizes recent studies on ubiquitin and ubiquitin-like modification of spliceosome components and discusses the relationship between spliceosome and the ubiquitin/26S proteasome pathway in plants.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Cell Biology
Chunbo Yang, Maria Georgiou, Robert Atkinson, Joseph Collin, Jumana Al-Aama, Sushma Nagaraja-Grellscheid, Colin Johnson, Robin Ali, Lyle Armstrong, Sina Mozaffari-Jovin, Majlinda Lako
Summary: Retinitis pigmentosa (RP) is the most common inherited retinal disease characterized by progressive photoreceptor degeneration, with mutations in PRPF genes causing dysregulation in global spliceosome function. Studies focus on key RP-PRPF genes, describing their roles in RNA splicing, impact of mutations on retinal cell function, and research in model species. Furthermore, investigations into PRPF functions beyond RNA splicing aim to provide a holistic understanding of PRPF-RP pathogenesis and develop novel therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Maureen V. Akinyi, Mikko J. Frilander
Summary: This article discusses the two different mechanisms for removing introns in eukaryotic species, the major spliceosome and minor spliceosome, and their interactions in shaping mRNA processing events in genes containing both major and minor introns.
FRONTIERS IN GENETICS
(2021)
Review
Oncology
Anthony J. Murphy, Alex H. Li, Peichao Li, Hong Sun
Summary: Alternative splicing plays a crucial role in diversifying the proteome and has significant implications in cancer development. Recent studies have highlighted the important roles of SR proteins in cancer progression. Understanding the spliceosome and its relationship to cancer has opened up new opportunities for therapeutic interventions based on alternative splicing.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mingtian Deng, Baobao Chen, Zifei Liu, Yongjie Wan, Dongxu Li, Yingnan Yang, Feng Wang
Summary: YBX1 plays important roles in maternal mRNA decay, alternative splicing, and transcriptional activity during early embryogenesis. These findings broaden our understanding of YBX1 functions.
CELL AND BIOSCIENCE
(2022)
Article
Cell Biology
Patrick A. Williams, Michael S. Krug, Emily A. McMillan, Jasmine D. Peake, Tara L. Davis, Simon Cocklin, Todd I. Strochlic
MOLECULAR BIOLOGY OF THE CELL
(2016)
Article
Biochemistry & Molecular Biology
Chelsea L. Gustafson, Nicole C. Parsley, Hande Asimgil, Hsiau-Wei Lee, Christopher Ahlbach, Alicia K. Michael, Haiyan Xu, Owen L. Williams, Tara L. Davis, Andrew C. Liu, Carrie L. Partch
Article
Biochemical Research Methods
Dene R. Littler, John R. Walker, Tara Davis, Leanne E. Wybenga-Groot, Patrick J. Finerty, Elena Newman, Farell Mackenzie, Sirano Dhe-Paganon
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2010)
Article
Biochemical Research Methods
Thanh G. Nguyen, Nicolette S. Honson, Steven Arns, Tara L. Davis, Sirano Dhe-Paganon, Suzana Kovacic, Nag S. Kumar, Tom A. Pfeifer, Robert N. Young
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
(2014)
Article
Biochemistry & Molecular Biology
Cecilia Eydoux, Silvia Spinelli, Tara L. Davis, John R. Walker, Alma Seitova, Sirano Dhe-Paganon, Alain De Caro, Christian Cambillau, Frederic Carriere
Article
Biochemistry & Molecular Biology
Tara L. Davis, John R. Walker, Hui Ouyang, Farrell MacKenzie, Christine Butler-Cole, Elena M. Newman, Elan Z. Eisenmesser, Sirano Dhe-Paganon
Article
Biochemistry & Molecular Biology
Tara L. Davis, John R. Walker, Abdellah Allali-Hassani, Sirlester A. Parker, Benjamin E. Turk, Sirano Dhe-Paganon
Article
Biochemistry & Molecular Biology
Vu Thai, Patricia Renesto, C. Andrew Fowler, Darin J. Browni, Tara Davis, Wanjun Gu, David D. Pollock, Dorothee Kern, Didier Raoult, Elan Z. Eisenmosser
JOURNAL OF MOLECULAR BIOLOGY
(2008)
Article
Biochemistry & Molecular Biology
Tara L. Davis, John R. Walker, Peter Loppnau, Christine Butler-Cole, Abdellah Allali-Hassani, Sirano Dhe-Paganon
Article
Biochemistry & Molecular Biology
Tara L. Davis, John R. Walker, Valerie Campagna-Slater, Patrick J. Finerty, Ragika Paramanathan, Galina Bernstein, Farrell MacKenzie, Wolfram Tempel, Hui Ouyang, Wen Hwa Lee, Elan Z. Eisenmesser, Sirano Dhe-Paganon
Article
Biochemistry & Molecular Biology
Caroline Rajiv, S. RaElle Jackson, Simon Cocklin, Elan Z. Eisenmesser, Tara L. Davis
BIOCHEMICAL JOURNAL
(2017)
Article
Biochemistry & Molecular Biology
Tara L. Davis, John R. Walker, Patrick J. Finerty, Farrell Mackenzie, Elena M. Newman, Sirano Dhe-Paganon
JOURNAL OF MOLECULAR BIOLOGY
(2007)
Article
Biochemistry & Molecular Biology
TL Davis, TM Bonacci, SR Sprang, AV Smrcka