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)
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
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)
Review
Biology
Miroslava Kretova, Tomas Selicky, Ingrid Cipakova, Lubos Cipak
Summary: Pre-mRNA splicing is a crucial process in eukaryotic cells to generate mature messenger RNAs for protein synthesis. The splicing process involves the removal of non-coding regions (introns) and joining of coding regions (exons) in pre-mRNAs. The spliceosome, composed of various proteins and factors, carries out the specific steps of splicing. Recent studies have revealed that post-translational modifications of splicing factors play significant roles in the regulation of pre-mRNA splicing, including phosphorylation, acetylation, methylation, ubiquitination, and sumoylation.
Article
Multidisciplinary Sciences
Xinyun Chen, Ying Liu, Chen Xu, Lina Ba, Zhuo Liu, Xiuya Li, Jie Huang, Ed Simpson, Hongyu Gao, Dayan Cao, Wei Sheng, Hanping Qi, Hongrui Ji, Maria Sanderson, Chen-Leng Cai, Xiaohui Li, Lei Yang, Jie Na, Kenichi Yamamura, Yunlong Liu, Guoying Huang, Weinian Shou, Ning Sun
Summary: The RNA-binding protein Quaking (QKI) plays a crucial role in cardiac development and contractile physiology through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology. Deficiency of QKI results in the failure of cardiomyocytes to mature into functional cells, highlighting its importance in cardiac pathophysiology.
NATURE COMMUNICATIONS
(2021)
Review
Plant Sciences
Yu Ling, Magdy M. Mahfouz, Shuangxi Zhou
Summary: The article reviews AS regulation in response to heat stress in different plant species and proposes that AS regulation participates in heat priming establishment and heat memory maintenance in plants. It suggests that pre-mRNA splicing variation is an important regulator of plant heat stress responses.
TRENDS IN PLANT SCIENCE
(2021)
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
Biotechnology & Applied Microbiology
Qiang Tang, Fulei Nie, Juanjuan Kang, Wei Chen
Summary: An innovative method called mRNALocater was proposed to detect the subcellular localization of eukaryotic mRNA by adopting a model fusion strategy. The method utilizes electron-ion interaction pseudopotential and pseudo k-tuple nucleotide composition to encode sequences and employs correlation coefficient filtering algorithm and feature forward search technology to mine hidden feature information, improving prediction accuracy. Results from independent dataset tests show promising performances for predicting eukaryotic mRNA sub-cellular localizations, making mRNALocater a powerful tool in practical applications.
Article
Biochemistry & Molecular Biology
Mehdi Ghram, Gavin Morris, Biljana Culjkovic-Kraljacic, Jean-Clement Mars, Patrick Gendron, Lucy Skrabanek, Maria Victoria Revuelta, Leandro Cerchietti, Monica L. Guzman, Katherine L. B. Borden
Summary: Aberrant splicing, a known contributor to malignancies, is usually attributed to splice-factor mutation. This study, however, discovered a mutation-independent mechanism for extensively reprogramming alternative splicing (AS) in acute myeloid leukemia (AML). The dysregulated expression of eukaryotic translation initiation factor eIF4E was found to increase selective splice-factor production, thereby affecting multiple spliceosome complexes and generating a splicing landscape that supported altered splice-site selection for hundreds of transcripts in AML patients with high-eIF4E expression.
Article
Cell Biology
Ananthanarayanan Kumar, Conny W. H. Yu, Juan B. Rodriguez-Molina, Xiao-Han Li, Stefan M. V. Freund, Lori A. Passmore
Summary: The translation provided describes a detailed study of the essential subunit Fip1 in the CPF/CPSF multiprotein complex, revealing the importance of its dynamics in coordinating cleavage and polyadenylation processes at the 3' end.
GENES & DEVELOPMENT
(2021)
Article
Immunology
Elena Putscher, Michael Hecker, Brit Fitzner, Nina Boxberger, Margit Schwartz, Dirk Koczan, Peter Lorenz, Uwe Klaus Zettl
Summary: This study found that genetic variants from MS risk loci affect pre-mRNA splicing. These findings substantiate the role of alternative splicing events in the genetics of MS. Further research on how disease-causing genetic variants modify the interactions between splicing regulatory sequence elements and RNA-binding proteins can help deepen our understanding of the genetic susceptibility to MS.
FRONTIERS IN IMMUNOLOGY
(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)
Editorial Material
Cell Biology
Yoseop Yoon, Yongsheng Shi
Summary: In this article, two independent studies successfully reconstituted the processing of human pre-mRNA 3' ends using defined components in vitro. These studies are of great importance for understanding the nature and essential components of this biological process.
GENES & DEVELOPMENT
(2022)
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
Biochemistry & Molecular Biology
Shan Liu, Wen-Jia Kang, Anna Abrimian, Jin Xu, Luca Cartegni, Susruta Majumdar, Patrick Hesketh, Alex Bekker, Ying-Xian Pan
Summary: The OPRM1 gene undergoes extensive alternative splicing to produce multiple splice variants with important pharmacological implications for the actions of opioid drugs. These variants can mediate distinct effects of various mu opioids and be targeted for the development of novel analgesics with potent efficacy against multiple types of pain while reducing side effects associated with traditional opiates.
Correction
Multidisciplinary Sciences
Federico Pelisch, Remi Sonneville, Ehsan Pourkarimi, Ana Agostinho, J. Julian Blow, Anton Gartner, Ronald T. Hay
NATURE COMMUNICATIONS
(2015)
Article
Biochemistry & Molecular Biology
Agustina P. Bertolin, Maximiliano J. Katz, Masato Yano, Berta Pozzi, Julieta M. Acevedo, Dalmiro Blanco-Obregon, Lautaro Gandara, Eleonora Sorianello, Hiroshi Kanda, Hideyuki Okano, Anabella Srebrow, Pablo Wappner
NUCLEIC ACIDS RESEARCH
(2016)
Article
Microbiology
Federico A. De Maio, Guillermo Risso, Nestor G. Iglesias, Priya Shah, Berta Pozzi, Leopoldo G. Gebhard, Pablo Mammi, Estefania Mancini, Marcelo J. Yanovsky, Raul Andino, Nevan Krogan, Anabella Srebrow, Andrea V. Gamarnik
Article
Biochemistry & Molecular Biology
Federico Pelisch, Triin Tammsalu, Bin Wang, Ellis G. Jaffray, Anton Gartner, Ronald T. Hay
Article
Biochemistry & Molecular Biology
Berta Pozzi, Laureano Bragado, Cindy L. Will, Pablo Mammi, Guillermo Risso, Henning Urlaub, Reinhard Luehrmann, Anabella Srebrow
NUCLEIC ACIDS RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
Berta Pozzi, Pablo Mammi, Laureano Bragado, Luciana E. Giono, Anabella Srebrow
Article
Cell Biology
Federico Pelisch, Laura Bel Borja, Ellis G. Jaffray, Ronald T. Hay
JOURNAL OF CELL SCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Berta Pozzi, Laureano Bragado, Pablo Mammi, Maria Florencia Torti, Nicolas Gaioli, Leopoldo G. Gebhard, Martin E. Garcia Sola, Rita Vaz-Drago, Nestor G. Iglesias, Cybele C. Garcia, Andrea Gamarnik, Anabella Srebrow
NUCLEIC ACIDS RESEARCH
(2020)
Article
Cell Biology
Luciana I. Gomez Acuna, Ezequiel Nazer, Santiago A. Rodriguez-Segui, Berta Pozzi, Valeria Buggiano, Luciano E. Marasco, Eneritz Agirre, Cody He, Mariano Allo, Alberto R. Kornblihtt
JOURNAL OF CELL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Andrea Princz, Federico Pelisch, Nektarios Tavernarakis
SCIENTIFIC REPORTS
(2020)
Editorial Material
Cell Biology
Samuel J. P. Taylor, Federico Pelisch
JOURNAL OF CELL BIOLOGY
(2020)
Article
Biology
Laura Bel Borja, Flavie Soubigou, Samuel J. P. Taylor, Conchita Fraguas Bringas, Jacqueline Budrewicz, Pablo Lara-Gonzalez, Christopher G. Sorensen Turpin, Joshua N. Bembenek, Dhanya K. Cheerambathur, Federico Pelisch
Article
Multidisciplinary Sciences
Bin Zhou, Tran Thi Nhu Thao, Donata Hoffmann, Adriano Taddeo, Nadine Ebert, Fabien Labroussaa, Anne Pohlmann, Jacqueline King, Silvio Steiner, Jenna N. Kelly, Jasmine Portmann, Nico Joel Halwe, Lorenz Ulrich, Bettina Salome Trueb, Xiaoyu Fan, Bernd Hoffmann, Li Wang, Lisa Thomann, Xudong Lin, Hanspeter Stalder, Berta Pozzi, Simone de Brot, Nannan Jiang, Dan Cui, Jaber Hossain, Malania M. Wilson, Matthew W. Keller, Thomas J. Stark, John R. Barnes, Ronald Dijkman, Joerg Jores, Charaf Benarafa, David E. Wentworth, Volker Thiel, Martin Beer
Summary: Research has shown that the D614G substitution in the spike protein of SARS-CoV-2 leads to increased binding and replication potential in humans, as well as significantly higher replication and transmissibility in different animal models, providing an explanation for the global prevalence of this variant in the COVID-19 pandemic.
Correction
Multidisciplinary Sciences
Federico Pelisch, Remi Sonneville, Ehsan Pourkarimi, Ana Agostinho, J. Julian Blow, Anton Gartner, Ronald T. Hay
NATURE COMMUNICATIONS
(2022)
Article
Biology
Samuel J. P. Taylor, Laura Bel Borja, Flavie Soubigou, Jack Houston, Dhanya K. Cheerambathur, Federico Pelisch
Summary: Phosphorylation is an important post-translational modification used for regulating protein localization and activity. Polo-like kinase 1 (PLK-1) is crucial for mitotic and meiotic cell divisions, but its specific roles and regulation in meiosis have been unclear. In this study, using C. elegans oocytes, we demonstrate that PLK-1 is involved in spindle assembly, chromosome alignment and segregation, and polar body extrusion during meiosis I. We also uncover the mechanisms of PLK-1 recruitment to meiotic chromosomes. Our findings reveal the essential functions of PLK-1 in oocyte meiosis and provide insights into its targeting mechanisms.