Article
Multidisciplinary Sciences
Yaron Strauch, Jenny Lord, Mahesan Niranjan, Diana Baralle
Summary: The SpliceAI algorithm, which utilizes deep neural networks, has a higher accuracy than other commonly used methods. This study improves the prediction ability of clinically relevant variants by including manually annotated alternatively spliced sites in the training data and suggests avenues for further performance improvements.
Article
Biochemical Research Methods
Aleksei Mironov, Stepan Denisov, Alexander Gress, Olga V. Kalinina, Dmitri D. Pervouchine
Summary: Tandem alternative splice sites (TASS) are a special class of alternative splicing events characterized by closely arranged splice sites. Our analysis of RNA-seq data from healthy human tissues expands the catalog of TASS, revealing tissue-specific expression, regulatory mechanisms, and impact on protein structure. The study suggests that both tissue-specific and cell-type-specific factors contribute to the regulation of miSS expression, with some affecting protein-protein interactions or protein core stability.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Armin Fuchs, Stefan Riegler, Zahra Ayatollahi, Nicola Cavallari, Luciana E. Giono, Barbara A. Nimeth, Krishna Mutanwad, Alois Schweighofer, Doris Lucyshyn, Andrea Barta, Ezequiel Petrillo, Maria Kalyna
Summary: The study revealed the importance of RNA interference in regulating gene expression, while its interactions with alternative splicing were not well understood. By using amiRNA to knockdown various splice variants of target genes, it was found that some transcript isoforms escaped degradation due to their nuclear localization. The isoforms of alternatively spliced genes that are nuclear localized and sensitive to NMD mask the action of RNA interference.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Yi-Ju Han, Kuo-Ming Lee, Guan-Hong Wu, Yu-Nong Gong, Avijit Dutta, Shin-Ru Shih
Summary: This study investigates the association between M segment splicing and pathogenicity in human influenza A viruses. The results demonstrate the important role of M2 protein in virus replication and pathogenicity, highlighting splicing regulation as a potential antiviral target.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Chunlei Tang, Qiang Xu, Jinren Zhao, Mingxing Yue, Jianfeng Wang, Xiaodong Wang, Zhensheng Kang, Xiaojie Wang
Summary: Alternative splicing is an important regulatory mechanism in plant resistance. This study identified a new effector protein, Pst_A23, produced by the wheat stripe rust pathogen, that targets the splicing process in wheat and suppresses the plant's defense response. The study also showed that Pst_A23 overexpression alters the splicing patterns of wheat genes and affects the production of functional transcripts, leading to decreased resistance to wheat stripe rust.
PLANT BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Adrian Cabezas-Fuster, Rosa Micol-Ponce, Sara Fontcuberta-Cervera, Maria Rosa Ponce
Summary: Efficient splicing requires a balance between high-fidelity splice-site (SS) selection and speed. In an Arabidopsis study, mutant alleles of the AGO1 and AXR6 genes were found to have novel splice sites that were recognized by the spliceosome, resulting in a mixture of wild-type and aberrant mature mRNAs. The study also characterized mutant alleles of the PRP8 gene, which showed a preference for the intact genuine splice sites of the AGO1 and AXR6 mutants, increasing splicing fidelity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Nicola de Prisco, Caitlin Ford, Nathan D. Elrod, Winston Lee, Lauren C. Tang, Kai-Lieh Huang, Ai Lin, Ping Ji, Venkata S. Jonnakuti, Lia Boyle, Maximilian Cabaj, Salvatore Botta, Katrin ounap, Karit Reinson, Monica H. Wojcik, Jill A. Rosenfeld, Weimin Bi, Kristian Tveten, Trine Prescott, Thorsten Gerstner, Audrey Schroeder, Chin-To Fong, Jaya K. George-Abraham, Catherine A. Buchanan, Andrea Hanson-Khan, Jonathan A. Bernstein, Aikaterini A. Nella, Wendy K. Chung, Vicky Brandt, Marko Jovanovic, Kimara L. Targoff, Hari Krishna Yalamanchili, Eric J. Wagner, Vincenzo A. Gennarino
Summary: Alternative polyadenylation (APA) generates different transcripts from the same gene by cleaving the pre-mRNA at different poly(A) sites. While most studies focus on APA within the 3' untranslated region (3' UTR), this study shows that CPSF6 insufficiency affects protein levels and leads to a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency alters poly(A) site usage in a pathway-specific manner.
Article
Multidisciplinary Sciences
Valter Bergant, Daniel Schnepf, Niklas de Andrade Kraetzig, Philipp Hubel, Christian Urban, Thomas Engleitner, Ronald Dijkman, Bernhard Ryffel, Katja Steiger, Percy A. A. Knolle, Georg Kochs, Roland Rad, Peter Staeheli, Andreas Pichlmair
Summary: Bergant et al. provide evidence that Influenza A viruses cause alternative polyadenylation of host mRNAs, leading to an attenuated phenotype in mice. This may constitute a common immune evasion mechanism employed by a variety of pathogenic viruses.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Sara Espinosa, Francesca De Bortoli, Xueni Li, John Rossi, Marisa E. Wagley, Hei-Yong G. Lo, J. Matthew Taliaferro, Rui Zhao
Summary: This study reveals that human PRPF39 serves as an alternative splicing factor by recruiting U1 snRNP to weak 5' ss. Additionally, it is found that TIA1 and LUC7L isoforms also play roles in this process. The similarities between yeast and human U1 snRNP structures support the use of yeast U1 snRNP as a model for understanding human alternative splicing mechanisms.
Review
Biotechnology & Applied Microbiology
Qiu Peng, Yujuan Zhou, Linda Oyang, Nayiyuan Wu, Yanyan Tang, Min Su, Xia Luo, Ying Wang, Xiaowu Sheng, Jian Ma, Qianjin Liao
Summary: Alternative pre-mRNA splicing plays a vital role in cancer by regulating cancer metabolism and immune response. Targeting splicing pathways or splicing-regulated metabolic pathways may be a promising strategy for cancer treatment.
Article
Biochemistry & Molecular Biology
Keiko Horiuchi, Takeshi Kawamura, Takao Hamakubo
Summary: The WTAP complex regulates alternative splicing by promoting exon skipping and intron retention, especially in AS events involving short introns/exons with higher GC content and weaker polypyrimidine-tract and branch points. Additionally, the interaction between WTAP and CBLL1 facilitates the recruitment of the 30-end processing complex, indicating an inhibitory mechanism in GC-rich sequences for AS and alternative polyadenylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Hematology
Zhiwei Ang, Luca Paruzzo, Katharina E. Hayer, Carolin Schmidt, Manuel Torres Diz, Feng Xu, Urvi Zankharia, Yunlin Zhang, Samantha Soldan, Sisi Zheng, Catherine D. Falkenstein, Joseph P. Loftus, Scarlett Y. Yang, Mukta Asnani, Patricia King Sainos, Vinodh Pillai, Emeline Chong, Marilyn M. Li, Sarah K. Tasian, Yoseph Barash, Paul M. Lieberman, Marco Ruella, Stephen J. Schuster, Andrei Thomas-Tikhonenko
Summary: Skipping of coding exons in CD19 and CD22 genes compromises immunotherapy response in B-cell malignancies. This study demonstrates that CD20 gene (MS4A1) also produces multiple mRNA isoforms with distinct untranslated regions. Modulating CD20 isoforms enhances CD20 expression and antibody-mediated cytotoxicity, potentially overcoming immunotherapy resistance.
Article
Genetics & Heredity
Adam P. P. Sage, Hyun Kyung Lee, Joshua Dalmann, Susan Lin, Simran Samra, Areesha Salman, Kate L. L. Del Bel, Wenhui Laura Li, Anna Lehman, Stuart E. E. Turvey, Cornelius F. F. Boerkoel, Phillip A. A. Richmond
Summary: In this study, a pathogenic intron 23 CLTC variant was identified, which is likely to generate or disrupt tandem splice sites and cause intellectual disability and behavioral problems. The variant was found to generate transcripts using cryptic proximal splice acceptors and undergo nonsense mediated mRNA decay. This is the first evidence of CLTC haploinsufficiency as a cause of CLTC-related disorder and the first evidence that the generation of tandem alternative splice sites causes CLTC-related disorder. Transcriptome-level analysis should be routinely pursued to define the pathogenicity of variants creating tandem alternative splice sites.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Namjeong Choi, Yongchao Liu, Jagyeong Oh, Jiyeon Ha, Claudia Ghigna, Xuexiu Zheng, Haihong Shen
Summary: The study identified SRSF2 and SRSF6 as regulatory factors for 5' splice-site selection of Bcl-x pre-mRNA, showing that a single binding motif or cluster is not their functional target. Mutagenesis of the 5' splice-site to a conserved or weaker score can limit the role of SRSF2 and SRSF6 in 5' splice-site activation.
Article
Cell Biology
Mauricio Gomes Pio, Maricel F. Molina, Sofia Siffo, Ana Chiesa, Carina M. Rivolta, Hector M. Targovnik
Summary: Mutations in TG gene can cause thyroid dysfunction and affect the health of newborns. A rare genetic mutation causing congenital hypothyroidism was identified in the study, contributing to a better understanding of the disease.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Immunology
Chung-Guei Huang, Li-Ang Lee, Tuan-Jen Fang, Hsueh-Yu Li, Chun-Ta Liao, Chung-Jan Kang, Tzu-Chen Yen, Kuo-Chien Tsao, Tse-Ching Chen, Shin-Ru Shih
JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION
(2020)
Article
Virology
Andrew Woodman, Kuo-Ming Lee, Richard Janissen, Yu-Nong Gong, Nynke H. Dekker, Shin-Ru Shih, Craig E. Cameron
JOURNAL OF VIROLOGY
(2019)
Article
Virology
Rei-Lin Kuo, Chi-Jene Chen, Robert Y. L. Wang, Hsing-I Huang, Ya-Han Lin, Ee-Hong Tam, Wen-Jung Tu, Shang-En Wu, Shin-Ru Shih
JOURNAL OF VIROLOGY
(2019)
Article
Biotechnology & Applied Microbiology
Yu-Nong Gong, Kuo-Chien Tsao, Guang-Wu Chen, Chung-Jung Wu, Yi-Hsiang Chen, Yi-Chun Liu, Shu-Li Yang, Yhu-Chering Huang, Shin-Ru Shih
JOURNAL OF GENERAL VIROLOGY
(2019)
Article
Plant Sciences
Ching-Tai Huang, Chen-Yiu Hung, Yu-Chia Hseih, Chia-Shiang Chang, Arul Balaji Velu, Yueh-Chia He, Yu-Lin Huang, Ting-An Chen, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Shin-Ru Shih, Avijit Dutta
Article
Pediatrics
Sheng-Yuan Ho, Cheng-Hsun Chiu, Yhu-Chering Huang, Chih-Jung Chen, Reyin Lien, Shih-Ming Chu, Chung-Guei Huang, Kuo-Chien Tsao, Shin-Ru Shih, Jen-Fu Hsu
PEDIATRICS AND NEONATOLOGY
(2020)
Article
Microbiology
Peng-Nien Huang, Hsiang-Ching Wang, Hui-Chen Hung, Sung-Nien Tseng, Teng-Yuan Chang, Min-Yuan Chou, Yu-Jen Chen, Yun-Ming Wang, Shin-Ru Shih, John Tsu-An Hsu
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2020)
Article
Biochemistry & Molecular Biology
Kuo-Ming Lee, Chih-Ching Wu, Shang-En Wu, Ya-Han Lin, Li-Ting Wang, Chun-Ru Chang, Peng-Nien Huang, Shin-Ru Shih, Rei-Lin Kuo
Review
Microbiology
Bo-Shiun Chen, Hou-Chen Lee, Kuo-Ming Lee, Yu-Nong Gong, Shin-Ru Shih
FRONTIERS IN MICROBIOLOGY
(2020)
Article
Immunology
Hsing- Huang, Jhao-Yin Lin, Hsiao-Chu Chiang, Pen-Nien Huang, Qing-Dong Lin, Shin-Ru Shih
JOURNAL OF INFECTIOUS DISEASES
(2020)
Review
Biochemistry & Molecular Biology
Yen-Chin Liu, Rei-Lin Kuo, Shin-Ru Shih
BIOMEDICAL JOURNAL
(2020)
Article
Microbiology
Chung-Guei Huang, Kuo-Ming Lee, Mei-Jen Hsiao, Shu-Li Yang, Peng-Nien Huang, Yu-Nong Gong, Tzu-Hsuan Hsieh, Po-Wei Huang, Ya-Jhu Lin, Yi-Chun Liu, Kuo-Chien Tsao, Shin-Ru Shih
JOURNAL OF CLINICAL MICROBIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Daming Zhou, Helen M. E. Duyvesteyn, Cheng-Pin Chen, Chung-Guei Huang, Ting-Hua Chen, Shin-Ru Shih, Yi-Chun Lin, Chien-Yu Cheng, Shu-Hsing Cheng, Yhu-Chering Huang, Tzou-Yien Lin, Che Ma, Jiandong Huo, Loic Carrique, Tomas Malinauskas, Reinis R. Ruza, Pranav N. M. Shah, Tiong Kit Tan, Pramila Rijal, Robert F. Donat, Kerry Godwin, Karen R. Buttigieg, Julia A. Tree, Julika Radecke, Neil G. Paterson, Piyada Supasa, Juthathip Mongkolsapaya, Gavin R. Screaton, Miles W. Carroll, Javier Gilbert-Jaramillo, Michael L. Knight, William James, Raymond J. Owens, James H. Naismith, Alain R. Townsend, Elizabeth E. Fry, Yuguang Zhao, Jingshan Ren, David Stuart, Kuan-Ying A. Huang
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2020)
Editorial Material
Medicine, General & Internal
Ville Peltola, Shin-Ru Shih, Kelvin Kai-Wang To
FRONTIERS IN MEDICINE
(2020)
Article
Cell Biology
Su-Jhen Hung, Yin-Mei Hsu, Sheng-Wen Huang, Huey-Pin Tsai, Leo Yi Yang Lee, Aeron C. Hurt, Ian G. Barr, Shin-Ru Shih, Jen-Ren Wang
JOURNAL OF BIOMEDICAL SCIENCE
(2020)