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)
Article
Multidisciplinary Sciences
Milan Hluchy, Pavla Gajduskova, Igor Ruiz de los Mozos, Michal Rajecky, Michael Kluge, Benedict-Tilman Berger, Zuzana Slaba, David Potesil, Elena Weiss, Jernej Ule, Zbynek Zdrahal, Stefan Knapp, Kamil Paruch, Caroline C. Friedel, Dalibor Blazek
Summary: RNA splicing, regulated by the spliceosome, is crucial for gene expression. CDK11 phosphorylates SF3B1 during spliceosome activation, which is important for spliceosome assembly and splicing regulation. Inhibition of CDK11 leads to defective spliceosome activation and disrupts the splicing process.
Article
Biochemistry & Molecular Biology
Laura Payan-Bravo, Sara Fontalva, Xenia Penate, Ildefonso Cases, Jose Antonio Guerrero-Martinez, Yerma Pareja-Sanchez, Yosu Odriozola-Gil, Esther Lara, Silvia Jimeno-Gonzalez, Carles Sune, Mari Cruz Munoz-Centeno, Jose C. Reyes, Sebastian Chavez
Summary: The study demonstrates that perturbations in prefoldin lead to transcriptional alterations in the human genome, particularly affecting splicing and expression of long genes with a high number of introns.
NUCLEIC ACIDS RESEARCH
(2021)
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
Chemistry, Multidisciplinary
Jure Borisek, Lorenzo Casalino, Andrea Saltalamacchia, Suzanne G. Mays, Luca Malcovati, Alessandra Magistrato
Summary: Pre-mRNA splicing, essential for gene expression, is carried out by the spliceosome, a complex molecular machinery responsible for accurately excising intronic sequences to produce mature mRNA. The spliceosome undergoes continuous compositional and conformational remodeling to ensure splicing fidelity. Recent advances in cryo-EM have provided near-atomic resolution structures of the spliceosome, shedding light on its complexity and function. Biochemical and genetic studies, combined with biomolecular simulations, are crucial for unraveling the molecular intricacies of splicing and exploring potential therapeutic strategies for diseases associated with splicing misregulation.
ACCOUNTS OF CHEMICAL RESEARCH
(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.
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)
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)
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
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
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
Chemistry, Medicinal
Riccardo Rozza, Pavel Janos, Alessandra Magistrato
Summary: RNA recognition motifs (RRMs) are important for RNA metabolism and gene expression regulation. Targeting RRM/RNA interfaces with small molecules is challenging due to their plasticity and fuzziness. In this study, an inhibitor was found to enhance the binding of pre-mRNA to U2AF2 and selectively induce cell death in leukemia cell lines. By applying and benchmarking static and dynamic docking approaches, the researchers elucidated the molecular basis of the inhibitor's effect and demonstrated the importance of considering dynamic effects when assessing binding modes of inhibitors targeting flexible RRMs and protein/protein/RNA interfaces.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Biochemistry & Molecular Biology
Francesca De Bortoli, Sara Espinosa, Rui Zhao
Summary: In eukaryotic cells, pre-mRNA splicing is catalyzed by the spliceosome, which undergoes dynamic rearrangements throughout the splicing cycle driven largely by eight DExD/H-box RNA helicases. Of particular interest are the four DEAH-box helicases that play a role in late-stage splicing and share structural similarities. Recent cryo-electron microscopy structures of the spliceosomal complexes have provided new insights into the structure and function of these DEAH-box helicases.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Maria J. R. Bezerra, Danielle M. N. Moura, Eden R. Freire, Fabiola B. Holetz, Christian R. S. Reis, Tallyta T. S. Monteiro, Adriana R. S. Pinto, Ning Zhang, Antonio M. Rezende, Antonio Pereira-Neves, Regina C. B. Q. Figueiredo, Christine Clayton, Mark C. Field, Mark Carrington, Osvaldo P. de Melo Neto
Summary: Translation in pathogenic protozoans of the family Trypanosomatidae involves multiple eIF4F-like complexes, with the EIF4E4/EIF4G3 and EIF4E3/EIF4G4 pairs being the most prominent. These complexes exhibit distinct protein partners and play important roles in gene expression and cell morphology. Knockdown studies revealed that EIF4E3/EIF4G4 are essential for viability and are involved in cytokinesis. The differential association of mRNAs with each complex was also identified through CLIP-seq analysis, further confirming their distinct functions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
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)
Article
Cell Biology
Quentin Defenouillere, Abdelkader Namane, John Mouaikel, Alain Jacquier, Micheline Fromont-Racine
MOLECULAR BIOLOGY OF THE CELL
(2017)
Article
Multidisciplinary Sciences
Pierre Plateau, Cosmin Saveanu, Roxane Lestini, Marc Dauplais, Laurence Decourty, Alain Jacquier, Sylvain Blanquet, Myriam Lazard
SCIENTIFIC REPORTS
(2017)
Article
Cell Biology
Agnieszka Tudek, Manfred Schmid, Marius Makaras, J. David Barrass, Jean D. Beggs, Torben Heick Jensen
Article
Biochemistry & Molecular Biology
Gonzalo I. Mendoza-Ochoa, J. David Barrass, Barbara R. Terlouw, Isabella E. Maudlin, Susana de Lucas, Emanuela Sani, Vahid Aslanzadeh, Jane A. E. Reid, Jean D. Beggs
Article
Biochemistry & Molecular Biology
Petr Tesina, Elisabeth Heckel, Jingdong Cheng, Micheline Fromont-Racine, Robert Buschauer, Lukas Kater, Birgitta Beatrix, Otto Berninghausen, Alain Jacquier, Thomas Becker, Roland Beckmann
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Elodie Zhang, Varun Khanna, Estelle Dacheux, Abdelkader Namane, Antonia Doyen, Maite Gomard, Bernard Turcotte, Alain Jacquier, Micheline Fromont-Racine
Article
Multidisciplinary Sciences
J. David Barrass, Gonzalo Mendoza-Ochoa, Isabella E. Maudlin, Emanuela Sani, Jean D. Beggs
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Article
Biochemistry & Molecular Biology
Gonzalo I. Mendoza-Ochoa, J. David Barrass, Isabella E. Maudlin, Jean D. Beggs
Article
Multidisciplinary Sciences
J. David Barrass, Jean D. Beggs
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Article
Cell Biology
Tommaso Villa, Mara Barucco, Maria-Jose Martin-Niclos, Alain Jacquier, Domenico Libri
Article
Biochemistry & Molecular Biology
Hanna Kratzat, Timur Mackens-Kiani, Michael Ameismeier, Mia Potocnjak, Jingdong Cheng, Estelle Dacheux, Abdelkader Namane, Otto Berninghausen, Franz Herzog, Micheline Fromont-Racine, Thomas Becker, Roland Beckmann
Summary: In eukaryotic translation, the termination and ribosome recycling phases are linked to the initiation of a new round of translation by factors such as ABCE1 and eIF3j. Cryo-EM analysis of native yeast and human ABCE1-containing pre-initiation complexes revealed their association with 43S and 48S initiation phases, showcasing a novel hybrid conformation and interaction network. This study provides valuable insights into the structural and functional roles of ABCE1 and eIF3j in translation initiation.
Article
Biochemistry & Molecular Biology
Andrada-Maria Birladeanu, Malgorzata Rogalska, Myrto Potiri, Vasiliki Papadaki, Margarita Andreadou, Dimitris L. Kontoyiannis, Joe D. Lewis, Zoi Erpapazoglou, Panagiota Kafasla
Summary: The cytosolic scaffold protein IQGAP1 regulates the subnuclear localization of spliceosome components and assists in stress-related splicing mechanisms in gastric cancer cells. It co-regulates cell cycle-related RNA splicing with hnRNPM, promoting gastric cancer cell proliferation. The study reveals a previously unknown link between stress signals and alternative splicing regulation.
Article
Endocrinology & Metabolism
Malgorzata E. Rogalska, Elizabeth Vafiadaki, Zoi Erpapazoglou, Kobra Haghighi, Lisa Green, Christos S. Mantzoros, Roger J. Hajjar, Michael Tranter, Ioannis Karakikes, Evangelia G. Kranias, Francesca Stillitano, Panagiota Kafasla, Despina Sanoudou
Summary: This study investigates the molecular mechanisms of arrhythmogenic cardiomyopathy (ACM) and provides insights into the role of alternative splicing in the pathogenesis of ACM. The findings suggest that aberrant splicing of key genes involved in calcium homeostasis may contribute to the increased risk of arrhythmia in ACM.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)