Article
Immunology
Jean -Baptiste Vulsteke, Vanessa Smith, Carolien Bonroy, Jan L. Lenaerts, Rita Derua, Wim A. Wuyts, Daniel Blockmans, Petra De Haes, Yves Piette, Ellen De Langhe, Xavier Bossuyt
Summary: This study aimed to identify and characterize new and rare anti-spliceosomal autoantibodies in SSc patients. By using IP-MS, the researchers found a new spliceosomal autoantigen called NineTeen Complex (NTC) and U5 RNP in SSc patients. This study suggests that major spliceosomal subcomplexes can be targeted by autoantibodies in systemic autoimmune diseases.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Pharmacology & Pharmacy
Satoshi Sato, Hiroyoshi Ariga, Hiroshi Maita
Summary: The spliceosome is a potential target for cancer therapy due to recurrent mutations in its components found in cancer. However, the lack of a robust cell-based approach has limited the discovery of small molecules that target the spliceosome. The use of a cell lysis buffer in BN-PAGE significantly improves the sensitivity and robustness of a genetic reporter for detecting spliceosome subunits, allowing for the discovery of small molecules that alter reporter activity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(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)
Article
Cell Biology
Bin Luo, Qingsong Jiang
Summary: This study explores the role of RNA-binding proteins (RBPs) in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). A total of 82 differentially expressed RBPs were identified, with functional analysis revealing their involvement in RNA transcription, translation, and degradation. The top 15 RBPs, including FBL, NOP58, and DDX10, may play a key role in promoting the osteogenic efficiency of BMSCs.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Microbiology
Francis R. Hopkins, Beatriz Alvarez-Rodriguez, George R. Heath, Kyriakoulla Panayi, Samantha Hover, Thomas A. Edwards, John N. Barr, Juan Fontana
Summary: Bunyaviruses are emerging RNA viruses that cause significant disease and economic burden and for which vaccines or therapies approved for humans are not available. The bunyavirus genome is wrapped up by the nucleoprotein (NP) and interacts with the viral polymerase, forming a ribonucleoprotein (RNP). This is the only form of the genome active for viral replication and assembly. However, until now how NPs are organized within an RNP was not known for any orthobunyavirus. Here, we purified RNPs from the prototypical orthobunyavirus, Bunyamwera virus, and employed microscopy approaches to show that the NP portion of the RNP was helical. We then combined our helical average with the known structure of an NP monomer, generating a pseudo-atomic model of this region. This arrangement allowed the RNPs to be highly flexible, which was critical for several stages of the viral replication cycle, such as segment circularization.
Article
Biochemistry & Molecular Biology
Julian Vosseberg, Daan Stolker, Samuel H. A. von der Dunk, Berend Snel
Summary: This study uses phylogenetic analyses to infer the evolutionary history of 145 proteins in the spliceosome. The results show that an abundance of ribosome-related proteins were added to the prokaryotic-derived core, and duplications of these proteins increased the overall complexity of the spliceosome. Most of the spliceosomal complexity originated after the spread of introns in the proto-eukaryotic genome. The reconstruction of early spliceosomal evolution provides insights into the emergence of complexes with many proteins during eukaryogenesis.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Jian Zhang, Ji Huang, Ke Xu, Peiqi Xing, Yue Huang, Zhaoqi Liu, Liang Tong, James L. Manley
Summary: SF3B1 is the most frequently mutated spliceosomal gene in cancer. A study identifies DHX15 as the critical helicase that functions with SUGP1 to cause the splicing defects of mutant SF3B1 in cancer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Juan L. Lopez-Canovas, Mercedes del Rio-Moreno, Helena Garcia-Fernandez, Juan M. Jimenez-Vacas, M. Trinidad Moreno-Montilla, Marina E. Sanchez-Frias, Victor Amado, Fernando L-Lopez, Marcos F. Fondevila, Ruben Ciria, Irene Gomez-Luque, Javier Briceno, Ruben Nogueiras, Manuel de la Mata, Justo P. Castano, Manuel Rodriguez-Peralvarez, Raul M. Luque, Manuel D. Gahete
Summary: Studies found that SF3B1 is overexpressed in hepatocellular carcinoma and is associated with tumor aggressiveness, oncogenic splicing variants expression, and decreased overall survival. Inhibition of SF3B1 genetically and/or pharmacologically may represent a promising novel therapeutic strategy.
Article
Multidisciplinary Sciences
Rui Bai, Ruixue Wan, Lin Wang, Kui Xu, Qiangfeng Zhang, Jianlin Lei, Yigong Shi
Summary: The study reveals the atomic features of the activated human minor spliceosome and the proteins that stabilize its conformation, providing a framework for understanding the mechanism of the minor spliceosome function.
Article
Biology
Kelren Rodrigues, Luiz Petroski, Paulo Utumi, Adriano Ferrasa, Roberto H. Herai
Summary: Splicing is a crucial post-transcriptional processing system that generates transcriptome diversity. The spliceosome machinery regulates splicing and is responsible for each step of RNA processing. However, the molecules and stages involved in splicing are currently scattered across different studies. Therefore, a curated atlas of spliceosome-related molecules and stages during RNA processing is essential for researchers to investigate this mechanism effectively.
LIFE SCIENCE ALLIANCE
(2023)
Article
Oncology
Benjamin Lebecque, Celine Bourgne, Chinmay Munje, Juliette Berger, Thomas Tassin, Pascale Cony-Makhoul, Agnes Guerci-Bresler, Hyacinthe Johnson-Ansah, Wei Liu, Sandrine Saugues, Andrei Tchirkov, David Vetrie, Mhairi Copland, Marc G. Berger
Summary: The study found that the alteration of spliceosome in chronic myeloid leukemia (CML) cells is associated with the development of the disease and exhibits intraclonal heterogeneity. Additionally, the combination of spliceosome-targeted drug and TKI can effectively treat CML without affecting healthy cells.
Article
Biochemistry & Molecular Biology
Fatimat Almentina Ramos Shidi, Audric Cologne, Marion Delous, Alicia Besson, Audrey Putoux, Anne-Louise Leutenegger, Vincent Lacroix, Patrick Edery, Sylvie Mazoyer, Remy Bordonne
Summary: Genetic diseases associated with microcephaly and developmental defects can be caused by pathogenic variants in the U4atac small nuclear RNA (snRNA). However, the molecular defects of most variants are still unknown. This study analyzed the consequences of RNU4ATAC compound heterozygous mutations on snRNPs formation and splicing in patients' cells, and found that the mutations induced splicing defects and affected the homeostasis and function of the Integrator complex.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yun-Sang Tang, Wai-Kin So, Ka-Leung Andy Ng, Ka-Pun Chris Mok, Pang-Chui Shaw
Summary: This study identified host heterogeneous nuclear ribonucleoprotein C as an interacting partner of influenza A virus nucleoprotein and confirmed its negative regulatory role in viral growth. The findings not only enhance our understanding of the influenza virus transmission mechanism but also provide a new research direction for the development of anti-influenza drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Asmaa Samy, Mehmet Kemal Ozdemir, Reda Alhajj
Summary: This study focuses on the relationship between SF3B1 and four types of cancer (MDS, AML, CLL, and BC). The results show that SF3B1 is more closely associated with hematologic malignancies (MDS, AML, CLL) than with breast cancer (BC). Different gene networks may be required to investigate the impact of mutant splicing factors on cancer development based on the type of cancer. Additionally, we summarized the set of genes and cellular pathways that are affected by aberrant splicing in cancerous cells based on the literature analyzed in this study.
SCIENTIFIC REPORTS
(2023)
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)
