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
Multidisciplinary Sciences
Xiaolin Wang, Jingxin Li, Xing Bian, Cheng Wu, Jinghan Hua, Shuhui Chang, Tianyi Yu, Hong Li, Yongxiang Li, Shanshan Hu, Ge Shan, Wenchu Lin
Summary: The study identified circURI7 as a circRNA with significantly higher expression in gastric cancer, which inhibits cell migration and invasion by modulating alternative splicing of genes involved in the process of cell migration, thus suppressing GC metastasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Zakaria Louadi, Kevin Yuan, Alexander Gress, Olga Tsoy, Olga Kalinina, Jan Baumbach, Tim Kacprowski, Markus List
Summary: Alternative splicing plays a crucial role in regulating the functional diversity of the proteome, but its isoform-specific effects on protein-protein interactions are often overlooked. By integrating various interaction information, researchers have developed a user-friendly database called DIGGER to study mechanistic consequences of alternative splicing, providing a valuable resource for exploring the functional role of individual exons on a network level.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Zhe Liu, Wei Wang, Xinru Li, Xiujuan Zhao, Hongyu Zhao, Wuritu Yang, Yongchun Zuo, Lu Cai, Yongqiang Xing
Summary: Alternative splicing plays an important role in zebrafish embryo development, especially during the maternal-to-zygotic transition process where it is highly abundant and dynamic. Splicing factors are expressed with developmental stage specificity, with a higher expression during the maternal-to-zygotic transition. The inclusion level of alternative splicing events performs well in cluster analysis and can be used as a novel parameter.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Qi Wen Chen, Qian Qian Cai, Ying Yang, Shu Dong, Yuan Yuan Liu, Zhong Yi Chen, Chun Lan Kang, Bing Qi, Yi Wei Dong, Wei Wu, Li Ping Zhuang, Ye Hua Shen, Zhi Qiang Meng, Xing Zhong Wu
Summary: This study reveals the important role and mechanism of long non-coding RNA BC in promoting tumor metastasis and influencing clinical prognosis of lung adenocarcinoma (LUAD). BC promotes growth, invasion, metastasis, and resistance to EGFR-targeted therapies in lung cancer by forming a splicing complex with nucleolin and hnRNPK. High expression of BC is associated with clinical progress and poor survival in LUAD.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jun Zhang, Shuaijun Chen, Sitian Wei, Shuangshuang Cheng, Rui Shi, Rong Zhao, Wei Zhang, Qi Zhang, Teng Hua, Dilu Feng, Zhicheng Yu, Hongbo Wang
Summary: This study found that circRAPGEF5 promotes rapid proliferation and confers resistance to ferroptosis in endometrial cancer (EC) cells through its interaction with RBFOX2. These findings provide new insights into the molecular mechanism by which circRNAs regulate ferroptosis, and suggest that the circRAPGEF5/RBFOX2 splicing axis could be a promising therapeutic target for treating EC.
Article
Biochemistry & Molecular Biology
Jialiang Li, Guangyue Li, Yige Qi, Yao Lu, Hao Wang, Ke Shi, Dangdang Li, Jinming Shi, Daniel B. Stovall, Guangchao Sui
Summary: In this study, SRSF5 was identified as a key regulator promoting the splicing of DMTF1 beta and gamma, while reducing DMTF1 alpha splicing. The expression of SRSF5 was positively correlated with the DMTF1 beta/alpha ratio in breast cancer samples.
Article
Oncology
Hongda Liu, Zheng Gong, Kangshuai Li, Qun Zhang, Zekuan Xu, Yunfei Xu
Summary: This study revealed that in colon adenocarcinoma tissue, the levels of MKNK2a decreased and MKNK2b increased, which were correlated with KRAS mutation and tumor size. The major splicing factor targeting MKNK2 in colon adenocarcinoma cells was confirmed to be SRSF1, whose phosphorylation and nuclear translocation were regulated by SRPK1/2 and PP1 alpha, subsequently affecting MKNK2 alternative splicing.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Zakaria Louadi, Maria L. Elkjaer, Melissa Klug, Chit Tong Lio, Amit Fenn, Zsolt Illes, Dario Bongiovanni, Jan Baumbach, Tim Kacprowski, Markus List, Olga Tsoy
Summary: Alternative splicing (AS) is a key aspect of gene regulation, and the tool NEASE has been developed to functionally characterize AS events by integrating pathways and protein-protein interaction annotations. NEASE has shown in four application cases its ability to identify pathways related to tissue identity and cell type development, as well as highlight splicing-related biomarkers, providing unique biological insights complementary to traditional pathways analysis.
Article
Plant Sciences
Hee Tae Lee, Hyo-Young Park, Keh Chien Lee, Jeong Hwan Lee, Jeong-Kook Kim
Summary: We investigated the transcriptomic changes in shoot apices during floral transition in Arabidopsis mutants of splicing factors AtU2AF65a and AtU2AF65b. AtU2AF65a mutants showed delayed flowering, while AtU2AF65b mutants exhibited accelerated flowering. RNA-seq analysis revealed that AtU2AF65a mutants had more differentially expressed genes compared to AtU2AF65b mutants. The gene FLOWERING LOCUS C (FLC), a major floral repressor, was significantly up- or down-regulated in the mutants. Additionally, the expression and alternative splicing patterns of several FLC upstream regulators were altered in the mutants. Our findings suggest that AtU2AF65a and AtU2AF65b splicing factors modulate FLC expression by affecting the expression or AS patterns of FLC upstream regulators, leading to different flowering phenotypes.
Review
Neurosciences
Roman Sloutsky, Margaret M. Stratton
Summary: Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a crucial regulator in the post-synapse during long-term potentiation, encoded by four genes in humans with alternative splicing leading to a diversity of proteins. Advances in sequencing technologies have led to the discovery of new CaMKII transcripts and suggest the adoption of a new naming scheme for CaMKII variants to better understand their biological implications.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Genetics & Heredity
Israel Ben-Dor, Crystal Pacut, Yuval Nevo, Eva L. Feldman, Benjamin E. Reubinoff
Summary: Expansion of the hexanucleotide repeat (HR) in the first intron of the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasians. The C9orf72-ALS/FTD patients share a common risk (R) haplotype. Characterizing the SNP signature and HR length of different C9orf72 haplotypes allows for the determination of the effects of expanded HR on C9orf72 gene expression and splicing.
Article
Biochemistry & Molecular Biology
Yu Jin, Maxim Ivanov, Anna Nelson Dittrich, Andrew D. L. Nelson, Sebastian Marquardt
Summary: This study identified a long noncoding RNA (FLAIL) in Arabidopsis that is associated with flowering. FLAIL directly interacts with target genes and affects their expression through RNA-DNA interactions and alternative splicing. The findings suggest that lncRNAs can regulate gene expression and organismal development as accessory components of the spliceosome.
Article
Biochemistry & Molecular Biology
Xue Wang, Changyun Ping, Puwen Tan, Chenguang Sun, Guang Liu, Tao Liu, Shuchun Yang, Yanmin Si, Lijun Zhao, Yongfei Hu, Yuyan Jia, Xiaoshuang Wang, Meili Zhang, Fang Wang, Dong Wang, Jia Yu, Yanni Ma, Yue Huang
Summary: The study reveals the critical role of RNA-binding proteins in pluripotency exit of embryonic stem cells, with hnRNPLL being identified as a key regulator of alternative splicing in ES cells. Its depletion leads to sustained expression of ES cell-preferred isoforms, resulting in differentiation deficiency and developmental defects. This highlights the potential application of targeting RBPs in controlling ES cell fate.
Article
Cardiac & Cardiovascular Systems
Carlos Marti-Gomez, Javier Larrasa-Alonso, Marina Lopez-Olaneta, Maria Villalba-Orero, Pablo Garcia-Pavia, Fatima Sanchez-Cabo, Enrique Lara-Pezzi
Summary: This study investigates the role of alternative splicing (AS) in heart disease and its relationship with heart development. It reveals the complex regulatory mechanisms and potential protein-protein interaction changes associated with AS changes, particularly in heart disease. The over-expression of PTBP1 is found to play a central role in regulating AS and is associated with cardiac hypertrophy and diastolic dysfunction.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Alessio Gerussi, Elvezia Maria Paraboschi, Claudio Cappadona, Chiara Caime, Eleonora Binatti, Laura Cristoferi, Rosanna Asselta, Pietro Invernizzi
Summary: This article discusses epigenetic modifications in Primary Biliary Cholangitis (PBC), including methylation, post-translational modifications of histone proteins, and non-coding RNA. The study found dysregulation of these modification levels, especially in immune cells, in PBC. The article also discusses the influence of X-chromosome abnormalities and abnormalities in X chromosome inactivation on the sex imbalance and pathogenesis of PBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Chiara Chiereghin, Michela Robusto, Valentina Massa, Pierangela Castorina, Umberto Ambrosetti, Rosanna Asselta, Giulia Solda
Summary: Hearing relies on the proper functioning of auditory hair cells and cytoskeletal structures. Diaphanous-related formins (DRFs) play important roles in metazoan development and the correct physiology of the reproductive and auditory systems. Mutations in DRF genes can cause sterility and impaired response to sound in fruit flies and vertebrates. In humans, defects in DIAPH1 and DIAPH3 are associated with different types of hearing loss, including deafness and auditory neuropathy.
Article
Clinical Neurology
Katina Aleksovska, Claudio L. A. Bassetti, Thomas Berger, Vanessa Carvalho, Joao Costa, Guenther Deuschl, Kristian S. Frederiksen, Joke Jaarsma, Teia Kobulashvili, Maurizio Leone, Lucia Pavlakova, Michele Romoli, Luca Vignatelli
Summary: This paper aims to establish a set of criteria for prioritizing topics for future European Academy of Neurology (EAN) guidelines. Through literature review, a Delphi consensus procedure, and voting, a set of approved criteria were determined, and the first 30 topics were selected. The process involved both a bottom-up approach with community involvement and a top-down approach with board member selection.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Immunology
Elina A. Tuovinen, Outi Kuismin, Leila Soikkonen, Timi Martelius, Meri Kaustio, Sari Hamalainen, Hanna Viskari, Jaana Syrjanen, Ulla Wartiovaara-Kautto, Kari K. Eklund, Janna Saarela, Markku Varjosalo, Juha Kere, Timo Hautala, Mikko R. J. Seppanen
Summary: The NF-κB family of transcription factors is important in cellular signaling pathways, and NFKB1 variants have been associated with CVID and immunodeficiency. However, the penetrance and prevalence of CVID are relatively low, while inflammatory manifestations are more common.
CLINICAL IMMUNOLOGY
(2023)
Review
Medicine, General & Internal
Renato Vellucci, Diego Fornasari
Summary: Tapentadol is an atypical opioid with improved gastrointestinal tolerability. This article provides an overview of opioid therapy in non-cancer pain, focusing on tapering of tapentadol in patients with chronic non-cancer pain. A flow chart is provided to guide clinicians in tapering tapentadol treatment based on individual patient characteristics and response to dosage reduction. Tapering strategies for tapentadol need further research.
CURRENT MEDICAL RESEARCH AND OPINION
(2023)
Article
Multidisciplinary Sciences
Chiara Chiereghin, Michela Robusto, Morag A. Lewis, Susana Caetano, Valentina Massa, Pierangela Castorina, Umberto Ambrosetti, Karen P. Steel, Stefano Duga, Rosanna Asselta, Giulia Solda
Summary: Diaphanous related formins are cytoskeletal proteins involved in actin elongation and microtubule stabilization. Defects in two diaphanous genes have been associated with hearing loss, and this study investigates the role of the third member, DIAPH2, in nonsyndromic hearing loss. A mutation in DIAPH2 was found to be linked to X-linked hearing loss in an Italian family. However, further studies are needed to fully understand the contribution of DIAPH2 to deafness.
Article
Clinical Neurology
Giulia Cardamone, Elvezia Maria Paraboschi, Giulia Solda, Giuseppe Liberatore, Valeria Rimoldi, Javier Cibella, Federica Airi, Veronica Tisato, Claudia Cantoni, Francesca Gallia, Donato Gemmati, Laura Piccio, Stefano Duga, Eduardo Nobile-Orazio, Rosanna Asselta
Summary: This study investigated the circRNA expression profile in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients and found a correlation with genetic and epigenetic background. Additionally, it discovered that MS-associated circRNA variants may impact disease pathogenesis by altering circRNA profiles.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Letter
Genetics & Heredity
Riccardo G. Borroni, Francesco Piscazzi, Mario Valenti, Valeria Rimoldi, Monica Barile, Paolo Bianchi, Rebecca Favaro, Alessandra Formai, Angelo Selicorni, Sofia Manara, Valeriano Vinci, Andrea G. Lania, Antonio Costanzo
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Immunology
Wenny Santaniemi, Pirjo Astrom, Virpi Glumoff, Nora Pernaa, Ella-Noora Tallgren, Sanna Palosaari, Antti Nissinen, Meri Kaustio, Outi Kuismin, Janna Saarela, Katariina Nurmi, Kari K. Eklund, Mikko R. J. Seppanen, Timo Hautala
Summary: In this study, the impact of a heterozygous NFKB1 c.C936T/p.R157X LOF variant on immunity in sterile fasciitis patients and their family members was explored. The variant resulted in reduced p50 or p105 protein levels and elevated IL-1 beta and IL-8 levels, potentially contributing to the high neutrophil counts observed during fasciitis episodes. The variant also led to reduced phosphorylation of p65/RelA in neutrophils, suggesting defective activation of canonical NF-kappa B, and compromised oxidative burst following activation of NF-kappa B-dependent mechanisms.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Oncology
Cesare Saitta, Ilaria De Simone, Vittorio Fasulo, Marinella Corbetta, Stefano Duga, Chiara Chiereghin, Federico Simone Colombo, Alessio Benetti, Roberto Contieri, Pier Paolo Avolio, Alessandro Uleri, Alberto Saita, Giorgio Ferruccio Guazzoni, Rodolfo Hurle, Piergiuseppe Colombo, Nicolo Maria Buffi, Paolo Casale, Giovanni Lughezzani, Rosanna Asselta, Giulia Solda, Massimo Lazzeri
Summary: Liquid biopsy (LB) is increasingly being explored as a non-invasive method for detecting prostate cancer (PCa). This study aimed to determine the rate of patients who were able to collect seminal fluid and evaluate the efficiency of the protocol in collecting prostate-derived cells. The results showed that only one third of locally advanced PCa patients were able to donate seminal fluid, with younger age and lower prostate volume being favorable predictors for semen collection.
Article
Medicine, General & Internal
Pui Y. Lee, Brad A. Davidson, Roshini S. Abraham, Blanche Alter, Juan I. Arostegui, Katherine Bell, Alexandre Belot, Jenna R. E. Bergerson, Timothy J. Bernard, Paul A. Brogan, Yackov Berkun, Natalie T. Deuitch, Dimana Dimitrova, Sophie A. Georgin-Lavialle, Marco Gattorno, Bodo Grimbacher, Hasan Hashem, Michael S. Hershfield, Rebecca N. Ichord, Kazushi Izawa, Jennifer A. Kanakry, Raju P. Khubchandani, Femke C. C. Klouwer, Evan A. Luton, Ada W. Man, Isabelle Meyts, Joris M. Van Montfrans, Seza Ozen, Janna Saarela, Gustavo C. Santo, Aman Sharma, Ariane Soldatos, Rachel Sparks, Troy R. Torgerson, Ignacio Leandro Uriarte, Taryn A. B. Youngstein, Qing Zhou, Ivona Aksentijevich, Daniel L. Kastner, Eugene P. Chambers, Amanda K. Ombrello
Summary: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. This study provides consensus statements for the evaluation and management of DADA2, a potentially fatal disease that requires early diagnosis and treatment.
Article
Biology
Roberto Gnavi, Ilenia Eboli, Paolo Emilio Alboini, Sandra D'Alfonso, Roberta Picariello, Giuseppe Costa, Maurizio Leone
Summary: The aim of this study was to evaluate the effect of the COVID-19 pandemic on the health outcomes of people with multiple sclerosis (PWMS). The study found that PWMS had a higher risk of hospitalization and admission to the ICU during the pandemic, but the increase in mortality was not statistically significant.
Review
Biochemistry & Molecular Biology
Francesca Salvatori, Elisabetta D'Aversa, Maria Luisa Serino, Ajay Vikram Singh, Paola Secchiero, Giorgio Zauli, Veronica Tisato, Donato Gemmati
Summary: Myocardial infarction (MI) is a leading cause of death in Western countries. Early diagnosis and treatment is vital to reduce complications and improve outcomes. Non-coding RNAs, especially microRNAs, play a significant role in the pathological processes of MI and post-MI phases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Adil Harroud, Pernilla J. Stridh, Jacob H. McCauley, Janna Saarela, Aletta M. R. van den Bosch, Hendrik Engelenburg, Ashley Beecham, Lars Alfredsson, Katayoun Alikhani, Lilyana Amezcua, Till F. M. Andlauer, Maria Ban, Lisa Barcellos, Nadia Barizzone, Tone Berge, Achim Berthele, Stefan Bittner, Steffan Bos, Farren B. S. Briggs, Stacy Caillier, Peter Calabresi, Domenico Caputo, David Carmona-Burgos, Paola Cavalla, Elisabeth Celius, Gabriel Cerono, Angel Chinea, Tanuja Chitnis, Ferdinando Clarelli, Manuel Comabella, Giancarlo Comi, Chris Cotsapas, Bruce C. A. Cree, Sandra D'Alfonso, Efthimios Dardiotis, Philip De Jager, Silvia Delgado, Benedicte Dubois, Sinah Engel, Federica Esposito, Marzena Fabis-Pedrini, Massimo Filippi, Kathryn Fitzgerald, Christiane Gasperi, Lissette Gomez, Refujia Gomez, Georgios Hadjigeorgiou, Joerg Hamann, Friederike Held, Roland Henry, Jan Hillert, Jesse Huang, Inge Huitinga, Talat Islam, Noriko Isobe, Maja Jagodic, Allan L. Kermode, Michael Khalil, Trevor Kilpatrick, Ioanna Konidari, Karim Kreft, Jeannette Lechner-Scott, Maurizio Leone, Felix Luessi, Sunny Malhotra, Ali Manouchehrinia, Clara Manrique, Filippo Martinelli-Boneschi, Andrea Martinez, Viviana Martinez-Maldonado, Elisabetta Mascia, Luanne Metz, Luciana Midaglia, Xavier Montalban, Jorge Oksenberg, Tomas Olsson, Annette Oturai, Kimmo Paakkonen, Grant P. Parnell, Nikolaos Patsopoulos, Margaret Pericak-Vance, Fredrik Piehl, Justin Rubio, Adam Santaniello, Silvia Santoro, Catherine Schaefer, Finn Sellebjerg, Hengameh Shams, Klementy Shchetynsky, Claudia Silva, Vasileios Siokas, Helle Sondergaard, Melissa Sorosina, Bruce Taylor, Marijne Vandebergh, Elena Vasileiou, Domizia Vecchio, Margarete Voortman, Howard Weiner, Dennis Wever, V. Wee Yong, David Hafler, Graeme Stewart, Alastair Compston, Frauke Zipp, Hanne Harbo, Bernhard Hemmer, An Goris, Joost Smolders, Stephen Hauser, Ingrid Kockum, Stephen Sawcer, Sergio Baranzini, Ingileif Jonsdottir, Yolanda Blanco, Sara Llufriu, Lohith Madireddy, Albert Saiz, Pablo Villoslada, Kari Stefansson, Hanne F. Harbo, Bernhard Hemmer, An Goris, Ingrid Kockum, Stephen J. Sawcer, Sergio E. Baranzini
Summary: Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS) and results in significant neurodegeneration. A genome-wide association study identified a significant association between the rs10191329 polymorphism in the DYSF-ZNF638 locus and MS severity. This polymorphism was also associated with earlier need for a walking aid and increased brain pathology. Another polymorphism in the DNM3-PIGC locus showed suggestive association with MS, and there was significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective effect of higher educational attainment in MS.