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
Biochemistry & Molecular Biology
Tea Anastasia Ruiz-Luis, Carlos Ortuno-Pineda, Jose Manuel Galindo-Rosales, Odila Saucedo-Cardenas, Jesus Valdes
Summary: ZO-1 alpha+ and ZO-1 alpha- proteins are expressed in different types of tight junctions. The factors involved in the splicing of the alpha exon are unknown. Our study reveals that the SRSF3-hairpin RNA interaction plays a crucial role in the early recognition of 3'ss for alpha exon activation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(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)
Article
Genetics & Heredity
Yi Cheng, Nan Huang, Qingqing Yin, Chao Cheng, Dong Chen, Chen Gong, Huihua Xiong, Jing Zhao, Jianhua Wang, Xiaoyu Li, Jing Zhang, Shuangshuang Mao, Kai Qin
Summary: Long non-coding RNA TP53TG1 plays an important role in the development of cervical cancer by inhibiting cell proliferation, inducing apoptosis, activating signaling pathways, and regulating the expression of RNA-binding protein genes.
FRONTIERS IN GENETICS
(2022)
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
Morgan Shine, Sarah E. Harris, Kendy A. Pellegrene, Adam H. Kensinger, Mihaela Rita Mihailescu, Jeffrey D. Evanseck, Patrick E. Lackey
Summary: Histone mRNA degradation is controlled by the 3' stem-loop and SLBP. The 3' stem-loop is trimmed by 3'hExo and uridylated by TUT7, creating partially degraded intermediates. Uridylation helps maintain the shape of the stem-loop and allows 3'hExo to maintain contact with the stem-loop after partial degradation.
Review
Biochemistry & Molecular Biology
Dirk Roos, Martin de Boer
Summary: Genetic mutations causing hereditary diseases often disrupt mRNA composition and protein stability, affecting synthesis, processing, or translation. Mutations in gene DNA regions like enhancers or promoters can impact mRNA processes. Understanding mRNA synthesis, processing, and translation is crucial for diagnosing genetic diseases effectively.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Oncology
Benoit Soubise, Yan Jiang, Nathalie Douet-Guilbert, Marie-Berengere Troadec
Summary: RBM22 is a gene that encodes an RNA-binding protein involved in RNA splicing, transcription, and gene regulation. Mutations and changes in dosage of RBM22 are associated with various diseases, particularly cancer. RBM22 has the potential to be a therapeutic target for specific diseases, including cancer.
Review
Biochemistry & Molecular Biology
Laining Zhang, Qidong Si, Kejie Yang, Wenwei Zhang, Thomas W. Okita, Li Tian
Summary: Subcellular mRNA localization is an important mechanism that regulates gene expression and establishes functional networks. Although our understanding of mRNA localization in plant cells is limited, the targeting of mRNA to the endoplasmic reticulum (ER) has been well studied in cereal grains.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kazuhiro Maeta, Manal Farea, Hisahide Nishio, Masafumi Matsuo
Summary: This study identified a novel antisense oligonucleotide called KMM001 that inhibits the maturation of myostatin mRNA, resulting in decreased myostatin protein levels. KMM001 also inhibits SMAD-mediated myostatin signaling and promotes human myoblast proliferation. These findings suggest that KMM001 has potential therapeutic applications for muscle-wasting conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Ainara Elorza, Yamile Marquez, Jorge R. Cabrera, Jose Luis Sanchez-Trincado, Maria Santos-Galindo, Ivo H. Hernandez, Sara Pico, Juan Diaz-Hernandez, Ramon Garcia-Escudero, Manuel Irimia, Jose J. Lucas
Summary: Correction of mis-splicing events is a promising therapeutic approach for neurological diseases caused by splicing-affecting mutations. Next-generation RNA sequencing has enabled the investigation of global mis-splicing in diseased tissue to identify key pathogenic mis-spliced genes. Our new intersect-RNA-seq approach captures pathogenic global mis-splicing in the Huntington's disease striatum.
Article
Cell Biology
Haroon Butt, Jeremie Bazin, Kasavajhala V. S. K. Prasad, Nourelislam Awad, Martin Crespi, Anireddy S. N. Reddy, Magdy M. Mahfouz
Summary: Abiotic stresses have significant impacts on plant growth, development, and crop productivity. The plant-specific splicing factor RS33 plays an important role in regulating pre-mRNA splicing and abiotic stress responses in rice.
Article
Biochemistry & Molecular Biology
Takahito Nakura, Atsufumi Ozoe, Yuka Narita, Masafumi Matsuo, Fumihiko Hakuno, Naoyuki Kataoka, Shin-Ichiro Takahashi
Summary: This study reveals that RbFox2 and SRSF3 proteins mediate exon 11 inclusion in rat hepatoma cells, with the UGCAUG sequence serving as a key regulator for exon 11 inclusion.
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)
Review
Cardiac & Cardiovascular Systems
Lisa M. Becker, Shiau-Haln Chen, Julie Rodor, Laura P. M. H. de Rooij, Andrew H. Baker, Peter Carmeliet
Summary: Endothelial cells play a crucial role in the human body but their heterogeneity poses challenges in therapy. Recent studies have revealed the diverse functions of endothelial cells and their roles in diseases, and proposed strategies to deal with this heterogeneity.
CARDIOVASCULAR RESEARCH
(2023)
Article
Genetics & Heredity
Adam M. Bournazos, Lisa G. Riley, Shobhana Bommireddipalli, Lesley Ades, Lauren S. Akesson, Mohammad Al-Shinnag, Stephen Alexander, Alison D. Archibald, Shanti Balasubramaniam, Yemima Berman, Victoria Beshay, Kirsten Boggs, Jasmina Bojadzieva, Natasha J. Brown, Samantha J. Bryen, Michael F. Buckley, Belinda Chong, Mark R. Davis, Ruebena Dawes, Martin Delatycki, Liz Donaldson, Lilian Downie, Caitlin Edwards, Matthew Edwards, Amanda Engel, Lisa J. Ewans, Fathimath Faiz, Andrew Fennell, Michael Field, Mary-Louise Freckmann, Lyndon Gallacher, Russell Gear, Himanshu Goel, Shuxiang Goh, Linda Goodwin, Bernadette Hanna, James Harraway, Megan Higgins, Gladys Ho, Bruce K. Hopper, Ari E. Horton, Matthew F. Hunter, Aamira J. Huq, Sarah Josephi-Taylor, Himanshu Joshi, Edwin Kirk, Emma Krzesinski, Kishore R. Kumar, Frances Lemckert, Richard J. Leventer, Suzanna E. Lindsey-Temple, Sebastian Lunke, Alan Ma, Steven Macaskill, Amali Mallawaarachchi, Melanie Marty, Justine E. Marum, Hugh J. McCarthy, Manoj P. Menezes, Alison McLean, Di Milnes, Shekeeb Mohammad, David Mowat, Aram Niaz, Elizabeth E. Palmer, Chirag Patel, Shilpan G. Patel, Dean Phelan, Jason R. Pinner, Sulekha Rajagopalan, Matthew Regan, Jonathan Rodgers, Miriam Rodrigues, Richard H. Roxburgh, Rani Sachdev, Tony Roscioli, Ruvishani Samarasekera, Sarah A. Sandaradura, Elena Savva, Tim Schindler, Margit Shah, Ingrid B. Sinnerbrink, Janine M. Smith, Richard J. Smith, Amanda Springer, Zornitza Stark, Samuel P. Strom, Carolyn M. Sue, Kenneth Tan, Tiong Y. Tan, Esther Tantsis, Michel C. Tchan, Bryony A. Thompson, Alison H. Trainer, Karin Van Spaendonck-Zwarts, Rebecca Walsh, Linda Warwick, Stephanie White, Susan M. White, Mark G. Williams, Meredith J. Wilson, Wui Kwan Wong, Dale C. Wright, Patrick Yap, Alison Yeung, Helen Young, Kristi J. Jones, Bruce Bennetts, Sandra T. Cooper
Summary: The study aims to provide standardized practices for PCR-based RNA diagnostics using clinically accessible specimens. The results show that RNA diagnostics can provide meaningful data for most genetic cases, allowing for variant reclassification and important applications in genetic counseling, clinical care, and prenatal counseling.
GENETICS IN MEDICINE
(2022)
Review
Cell Biology
Marina Reixachs-Sole, Eduardo Eyras
Summary: High-throughput sequencing of cellular RNAs has revealed the wide-ranging impact of alternative splicing on the transcriptome, and differential production of transcript isoforms is recognized as a critical mechanism in cell differentiation, organismal development, and disease. However, the extent of the effect of alternative splicing on protein production and cellular function is still a matter of debate. Recent advances in experimental and computational approaches have shed light on how molecular changes in the RNA processing pathway can affect protein production and function.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Article
Biochemistry & Molecular Biology
Nele Hug, Stuart Aitken, Dasa Longman, Michaela Raab, Hannah Armes, Abigail R. Mann, Ana Rio-Machin, Jude Fitzgibbon, Kevin Rouault-Pierre, Javier F. Caceres
Summary: The RNA helicase DHX34 plays a dual role in both nonsense-mediated decay (NMD) and pre-mRNA splicing, and its loss may contribute to the development of acute myeloid leukemia (AML) by regulating the splicing of AML-associated pre-mRNAs.
Article
Medical Laboratory Technology
Juan M. Jimenez-Vacas, Antonio J. Montero-Hidalgo, Enrique Gomez-Gomez, Prudencio Saez-Martinez, Antonio C. Fuentes-Fayos, Adria Closa, Teresa Gonzalez-Serrano, Ana Martinez-Lopez, Rafael Sanchez-Sanchez, Pedro P. Lopez-Casas, Andre Sarmento-Cabral, David Olmos, Eduardo Eyras, Justo P. Castano, Manuel D. Gahete, Raul M. Luque
Summary: Prostate cancer is a major cause of cancer-related deaths in men, and there is a need for novel molecular targets for treatment. The study found that RB22, a key spliceosome component, is down-regulated in prostate cancer and is associated with tumor aggressiveness. Overexpression of RB22 can reduce the aggressiveness of prostate cancer by impacting the splicing of numerous genes and the regulation of cell cycle. Targeting negative regulators of RB22 expression/activity could be a novel therapeutic strategy for prostate cancer.
TRANSLATIONAL RESEARCH
(2023)
Article
Biology
Alba Navarro-Romero, Lorena Galera-Lopez, Paula Ortiz-Romero, Alberto Llorente-Ovejero, Lucia De los Reyes-Ramirez, Iker Bengoetxea de Tena, Anna Garcia-Elias, Aleksandra Mas-Stachurska, Marina Reixachs-Sole, Antoni Pastor, Rafael de la Torre, Rafael Maldonado, Begona Benito, Eduardo Eyras, Rafael Rodriguez-Puertas, Victoria Campuzano, Andres Ozaita
Summary: Williams-Beuren syndrome (WBS) is a rare genetic disorder characterized by intellectual disability and hypersocial behavior. This study suggests that modulation of the endocannabinoid system could be a potential therapeutic approach for treating WBS, as it improves both social and cognitive phenotypes in a mouse model.
Article
Developmental Biology
Olga Zaytseva, Naomi C. Mitchell, Damien Muckle, Caroline Delandre, Zuqin Nie, Janis K. Werner, John T. Lis, Eduardo Eyras, Ross D. Hannan, David L. Levens, Owen J. Marshall, Leonie M. Quinn
Summary: FUBP1 and Psi, members of the FUSE Binding Protein family, regulate gene transcription by binding to single-stranded DNA and RNA, promoting cell growth and division. Psi activates Myc and stg to promote cell proliferation, while repressing the transcription of tok, a growth inhibitor.
Article
Biology
Hjoerleifur Einarsson, Marco Salvatore, Christian Vaagenso, Nicolas Alcaraz, Jette Bornholdt, Sarah Rennie, Eduardo Eyras, Robin Andersson
Summary: This study investigates the relationship between the sequence and transcription start site architectures of promoters and their expression variability across human individuals. The results show that expression variability can be largely explained by a promoter's DNA sequence and its binding sites for specific transcription factors. Additionally, the study reveals a trade-off between stability and plasticity for different types of genes.
Review
Biochemical Research Methods
Pablo Acera Mateos, You Zhou, Kathi Zarnack, Eduardo Eyras
Summary: The development of new high-throughput techniques has played a crucial role in discovering the properties of RNA modifications with the help of machine learning. Despite the challenges, this review provides a comprehensive survey of machine learning methods for detecting RNA modifications and strategies for training and testing these methods. The review also highlights current challenges and open questions in RNA modification analysis, and emphasizes the potential of machine learning in addressing these limitations.
BRIEFINGS IN BIOINFORMATICS
(2023)
Letter
Cardiac & Cardiovascular Systems
Julie Rodor, Shiau-Haln Chen, Andrew H. Baker
CARDIOVASCULAR RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Laura Monaghan, Dasa Longman, Javier F. Caceres
Summary: mRNA surveillance pathways play a crucial role in maintaining accurate gene expression and translation homeostasis. Studying these pathways can help us understand how cellular mRNA levels are regulated, how defective mRNAs are eliminated, and how dysregulation can contribute to human disease.
Article
Microbiology
Alicia Vachon, Grace E. Seo, Nishi H. Patel, Carla S. Coffin, Eric Marinier, Eduardo Eyras, Carla Osiowy
Summary: This study evaluated the composition and proportionality of serum hepatitis B virus (HBV) RNA transcripts in chronic hepatitis B (CHB) infection patients using PCR-cDNA nanopore sequencing. The results showed that HBV pregenomic RNA (pgRNA) was the most frequently observed transcript isoform, followed by other pgRNA spliced variants, 3' truncated variants and HBx mRNA. The type and proportion of transcripts were influenced by HBV genotype and HBeAg status. The study demonstrated the utility of long-read sequencing for studying the serum HBV transcriptome.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Adria Closa, Marina Reixachs-Sole, Antonio C. Fuentes-Fayos, Katharina E. Hayer, Juan L. Melero, Fabienne R. S. Adriaanse, Romy S. Bos, Manuel Torres-Diz, Stephen P. Hunger, Kathryn G. Roberts, Charles G. Mullighan, Ronald W. Stam, Andrei Thomas-Tikhonenko, Justo P. Castano, Raul M. Luque, Eduardo Eyras
Summary: This study conducted a comprehensive multicohort analysis to explore the molecular mechanisms underlying the poor prognosis in infant B-cell acute lymphoblastic leukemia (B-ALL) patients. They identified gene fusions and RNA splicing alterations that may contribute to the observed outcomes. Specifically, they found that upregulation of the splicing factor SRRM1 is associated with high risk and affects cell survival, proliferation, and invasion. These findings suggest a potential convergent mechanism of aberrant RNA processing in infant B-ALL.
Meeting Abstract
Hematology
Talia Velasco, Juan Trincado, Meritxell Vinyoles, Adria Closa, Oscar Molina, Clara Bueno, Eduardo Eyras, Holger Heyn, Pablo Menendez
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Ivan de la Rubia, Akanksha Srivastava, Wenjing Xue, Joel A. Indi, Silvia Carbonell-Sala, Julien Lagarde, M. Mar Alba, Eduardo Eyras
Summary: Nanopore sequencing enables efficient and unbiased measurement of transcriptomes. RATTLE, a tool that performs reference-free reconstruction and quantification of transcripts using only Nanopore reads, accurately determines transcript sequences and abundances. It demonstrates good scalability with the number of transcripts, based on simulated and experimental data from multiple sources.