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.
Article
Biotechnology & Applied Microbiology
Annette D'Arqom, Tiwaporn Nualkaew, Natee Jearawiriyapaisarn, Ryszard Kole, Saovaros Svasti
Summary: Restoration of correct splicing of beta(IVS2-654)-globin pre-mRNA was successfully achieved in thalassemic mice using engineered U7.BP+623 snRNA, but a high level of truncated U7.BP+623 snRNA was also observed. Differences in the processing of modified U7 snRNA between human and mouse constructs hindered the evaluation of pathological improvement in the mouse model.
HUMAN GENE THERAPY
(2021)
Article
Multidisciplinary Sciences
Praveen Kumar Kathare, Ruijiao Xin, Abirama Sundari Ganesan, Viviana M. June, Anireddy S. N. Reddy, Enamul Huq
Summary: Light signals have significant effects on the physiology, growth, and development of plants. SWAP1, an RNA-binding splicing factor, regulates light-regulated alternative splicing by interacting with other splicing factors and photoactivated phyB.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Carlos A. Nino, Rossella Scotto di Perrotolo, Simona Polo
Summary: This review summarizes the cancer hotspot mutations in spliceosome components, focusing on the effects of mutations in U1 snRNA, SF3B1, and U2AF1 on splice site selection and cancer development.
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)
Review
Plant Sciences
Praveen Kumar Kathare, Enamul Huq
Summary: The article summarizes the role of phytochromes in regulating plant growth and development, particularly in the regulation of pre-mRNA splicing process.
CURRENT OPINION IN PLANT BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhenwei Zhang, Norbert Rigo, Olexandr Dybkov, Jean-Baptiste Fourmann, Cindy L. Will, Vinay Kumar, Henning Urlaub, Holger Stark, Reinhard Luehrmann
Summary: During the splicing process, the integration of U2 small nuclear ribonucleoprotein into the spliceosomal A complex is facilitated by the DEAD-box helicase Prp5. Research reveals that the RNA duplex formed by U2 small nuclear RNA is proofread by Prp5, and the U2-BS helix is formed in the pre-A complex. The study further shows a large-scale remodelling of U1 and U2 snRNPs and how the binding of Hsh155(HEAT) triggers closure, disrupting Prp5 binding.
Article
Genetics & Heredity
Brian Joseph, Eric C. Lai
Summary: The EJC not only suppresses re-splicing in Drosophila genes, but also prevents new splicing events on already spliced segments to maintain the integrity of the transcriptome.
Article
Biochemistry & Molecular Biology
Nicole M. Martinez, Amanda Su, Margaret C. Burns, Julia K. Nussbacher, Cassandra Schaening, Shashank Sathe, Gene W. Yeo, Wendy Gilbert
Summary: This study investigates the pseudouridylation of mRNAs in their life cycle and reveals its potential regulatory functions. By analyzing chromatin-associated RNA from human cells, pseudouridines were found in nascent pre-mRNA at regions associated with alternative splicing and near splice sites. In vitro splicing assays demonstrate the direct effect of individual endogenous pre-mRNA pseudouridines on splicing efficiency. The study establishes a potential for cotranscriptional pre-mRNA pseudouridylation to regulate human gene expression via alternative pre-mRNA processing.
Article
Biochemistry & Molecular Biology
Eliezra Glasser, Debanjana Maji, Giulia Biancon, Anees Mohammed Keedakkatt Puthenpeedikakkal, Chapin E. Cavender, Toma Tebaldi, Jermaine L. Jenkins, David H. Mathews, Stephanie Halene, Clara L. Kielkopf
Summary: This study reveals the flexibility of U2AF2 in recognizing polypyrimidine tracts of nascent transcripts and the tolerance of nucleotide substitutions at the central position of the Py tract. The results highlight the importance of RNA flexibility for protein recognition and provide insights into the relationship between splice site motifs and pre-mRNA splicing efficiencies.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Klara Klimesova, Hana Petrzilkova, Cyril Barinka, David Stanek
Summary: SART3 is a multifunctional protein involved in multiple steps of gene expression, including the assembly and recycling of the spliceosomal U4/U6 snRNP. This study demonstrates that SART3 interacts with the 12S U2 snRNP through its N-terminal HAT domain. Furthermore, it associates with the post-splicing complex containing U2 and U5 snRNP components, and also interacts with the RNA helicase DHX15. The proposed model suggests that SART3 protects and initiates the recycling of U6 snRNA in the post-splicing complex.
JOURNAL OF CELL SCIENCE
(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
Endocrinology & Metabolism
Kazuhisa Akiba, Yukihiro Hasegawa, Yuko Katoh-Fukui, Miho Terao, Shuji Takada, Tomonobu Hasegawa, Maki Fukami, Satoshi Narumi
Summary: This study demonstrates that the c.143-83A>G variant leads to splicing disruption, resulting in morphological and functional abnormalities in the pituitary gland. The findings provide valuable insights into the role of POU1F1/Pou1f1 transcripts in pituitary development.
Review
Oncology
Sunkyung Choi, Namjoon Cho, Eun-Mi Kim, Kee K. Kim
Summary: Alternative pre-mRNA splicing plays a critical role in generating multiple mRNA and increasing protein diversity. Specific splicing isoforms have been found to be important in cellular processes, particularly in regulating cell numbers. Abnormal expression of splicing isoforms and factors, as well as disruptions in splicing caused by genetic mutations, are implicated in cancer development and progression. Alternative splicing has potential as a therapeutic target for cancer.
CANCER CELL INTERNATIONAL
(2023)
Article
Biology
Matthew T. Parker, Beth K. Soanes, Jelena Kusakina, Antoine Larrieu, Katarzyna Knop, Nisha Joy, Friedrich Breidenbach, Anna Sherwood, Geoffrey J. Barton, Sebastian M. Fica, Brendan H. Davies, Gordon G. Simpson, Jonathan P. Staley
Summary: Alternative splicing is associated with the evolution of complex eukaryotes. The m(6)A modification of U6 snRNA plays a crucial role in splicing accuracy and efficiency. The sequence composition of splice sites and the cooperative roles of U5 and U6 snRNA are important in splice site selection. U6 snRNA m(6)A modification influences the usage of 3' splice sites. Two major classes of 5' splice site were identified in diverse eukaryotes.
Article
Biochemistry & Molecular Biology
John W. Hardin, Chandani Warnasooriya, Yasushi Kondo, Kiyoshi Nagai, David Rueda
NUCLEIC ACIDS RESEARCH
(2015)
Article
Biochemistry & Molecular Biology
Stefan Luzi, Yasushi Kondo, Elise Bernard, Lukas K. J. Stadler, Marina Vaysburd, Greg Winter, Philipp Holliger
PROTEIN ENGINEERING DESIGN & SELECTION
(2015)
Article
Multidisciplinary Sciences
Thi Hoang Duong Nguyen, Wojciech P. Galej, Xiao-chen Bai, Chris Oubridge, Andrew J. Newman, Sjors H. W. Scheres, Kiyoshi Nagai
Article
Multidisciplinary Sciences
Wojciech P. Galej, Max E. Wilkinson, Sebastian M. Fica, Chris Oubridge, Andrew J. Newman, Kiyoshi Nagai
Article
Multidisciplinary Sciences
Sebastian M. Fica, Chris Oubridge, Wojciech P. Galej, Max E. Wilkinson, Xiao-Chen Bai, Andrew J. Newman, Kiyoshi Nagai
Article
Biochemistry & Molecular Biology
Anne-Marie M. Van Roon, Chris Oubridge, Eiji Obayashi, Benedetta Sposito, Andrew J. Newman, Bertrand Seraphin, Kiyoshi Nagai
Article
Biology
Yvonne Vercoulen, Yasushi Kondo, Jeffrey S. Iwig, Axel B. Janssen, Katharine A. White, Mojtaba Amini, Diane L. Barber, John Kuriyan, Jeroen P. Roose
Article
Biology
Pradeep Bandaru, Neel H. Shah, Moitrayee Bhattacharyya, John P. Barton, Yasushi Kondo, Joshua C. Cofsky, Christine L. Gee, Arup K. Chakraborty, Tanja Kortemme, Rama Ranganathan, John Kuriyan
Article
Medicine, Research & Experimental
Pradeep Bandaru, Yasushi Kondo, John Kuriyan
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2019)
Article
Multidisciplinary Sciences
William Y. C. Huang, Steven Alvarez, Yasushi Kondo, Young Kwang Lee, Jean K. Chung, Hiu Yue Monatrice Lam, Kabir H. Biswas, John Kuriyan, Jay T. Groves
Article
Multidisciplinary Sciences
Sebastian M. Fica, Chris Oubridge, Max E. Wilkinson, Andrew J. Newman, Kiyoshi Nagai
Article
Multidisciplinary Sciences
Yasushi Kondo, Jana Ognjenovic, Saikat Banerjee, Deepti Karandur, Alan Merk, Kayla Kulhanek, Kathryn Wong, Jeroen P. Roose, Sriram Subramaniam, John Kuriyan
Review
Crystallography
Adelaine Kwun-Wai Leung, Yasushi Kondo, Daniel A. Pomeranz Krummel, Jade Li, Stephen R. Price, Anne-Marie M. van Roon
Summary: This review provides an overview of crystal structures solved by the Nagai group, which have advanced our understanding of the spliceosome mechanism by utilizing various strategies for crystal packing design.