Review
Biochemistry & Molecular Biology
Giambattista Marotta, Filippo Basagni, Michela Rosini, Anna Minarini
Summary: Fyn kinase plays crucial roles in cell signaling pathways, involved in various biological functions in cancer and the nervous system. Research on Fyn inhibitors has made significant progress and offers promising opportunities for therapeutic intervention in neurodegenerative diseases.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chu-Yi Zhang, Xiao Xiao, Zhuohua Zhang, Zhonghua Hu, Ming Li
Summary: Transcriptomic and long-read sequencing analyses have revealed alternative splicing characteristics of schizophrenia risk genes, identifying new spliced isoforms and providing examples for investigating these isoforms in vitro and in vivo.
MOLECULAR PSYCHIATRY
(2022)
Article
Genetics & Heredity
Li Zhang, Lu Wang, Han Xiao, Hui Gan, Hui Chen, Shuyue Zheng, Dan Jian, Xuan Zhai, Ning Jiang, Zhao Jing, Ping Liang
Summary: This study found that Fyn expression is increased in human and rat cerebral tissues after ICH, Fyn knockdown can prevent secondary cerebral damage following ICH, inhibition of Fyn has minimal effects on inflammatory responses but exerts neuroprotective effects on apoptosis. Fyn perturbs ICH-induced cell apoptosis by interacting with and phosphorylating (Ser616) Drp1 in a rat ICH model.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Multidisciplinary Sciences
Zihan Tang, Yanyan Xu, Yun Tan, Hui Shi, Peipei Jin, Yunqi Li, Jialin Teng, Honglei Liu, Haoyu Pan, Qiongyi Hu, Xiaobing Cheng, Junna Ye, Yutong Su, Yue Sun, Jianfen Meng, Zhuochao Zhou, Huihui Chi, Xuefeng Wang, Junling Liu, Yong Lu, Feng Liu, Jing Dai, Chengde Yang, Saijuan Chen, Tingting Liu
Summary: Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection. The E protein is found to be associated with coagulation disorders in COVID-19 patients and directly enhances platelet activation and thrombosis through a CD36/p38 MAPK/NF-kB signaling axis.
NATURE COMMUNICATIONS
(2023)
Review
Plant Sciences
Long Wang, Fan Xu, Feng Yu
Summary: Plants have developed adaptation mechanisms to respond to environmental signals, and receptors/sensors play a crucial role in recognizing these signals. RNA metabolism is also important in regulating gene expression and protein synthesis. Recent advances in RNA biotechnology have shed light on the roles of RNA metabolism, particularly alternative splicing and translation, in response to environmental signals. Understanding these mechanisms at the posttranscriptional level improves our ability to breed stress-tolerant plants for changing environments.
PLANT CELL AND ENVIRONMENT
(2023)
Review
Biochemical Research Methods
Jiashu Liu, Cui-Xiang Lin, Xiaoqi Zhang, Zongxuan Li, Wenkui Huang, Jin Liu, Yuanfang Guan, Hong-Dong Li
Summary: Alternative splicing (AS), a key pathway for transcriptional regulation, has been shown to be associated with complex diseases. Computational approaches for detecting disease-associated AS events have been developed. This review discusses the metrics used for characterizing AS events quantitatively. It also reviews and discusses three types of methods for detecting disease-associated splicing events: differential splicing analysis, aberrant splicing detection, and splicing-related network analysis. Additionally, methods for detecting genetic variants that potentially regulate splicing are described. Experimental comparisons are conducted to illustrate the performance of each method. The limitations of these methods are discussed, as well as potential ways to address them. This review aims to provide a systematic understanding of computational approaches for analyzing disease-associated splicing.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Multidisciplinary Sciences
Jiancheng Xue, Tie Ma, Xiaowen Zhang
Summary: The dysregulation of alternative splicing in cancer is commonly observed and serves as a crucial indicator for cancer progression and therapy. Transformer 2 (TRA2), a nuclear RNA binding protein, consisting of TRA2A and TRA2B, has been found to be dysregulated in various types of tumors. It modulates the proliferation, migration, invasion, and chemotherapy resistance of cancer cells by altering the alternative splicing of cancer-related genes. This review focuses on the role of TRA2 in tumorigenesis and metastasis, and discusses the potential molecular mechanisms by which TRA2 influences these processes through controlling alternative splicing. We propose that TRA2A is a novel biomarker and therapeutic target for cancer progression and therapy.
Article
Plant Sciences
Grant W. de Jong, Keith L. Adams
Summary: Polyploidy has had a significant impact on the evolution of flowering plants. Allopolyploids, particularly Brassica napus, show extensive changes in gene expression and alternative splicing patterns when infected with the fungal pathogen Sclerotinia sclerotiorum. RNA-sequencing analyses reveal these differences and their role in enhancing the defense response against the pathogen.
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
Cell Biology
Tony J. Zheng, Elizabeth R. Lofurno, Alexander R. Melrose, Hari Hara Sudhan Lakshmanan, Jiaqing Pang, Kevin G. Phillips, Meghan E. Fallon, Tia C. L. Kohs, Anh T. P. Ngo, Joseph J. Shatzel, Monica T. Hinds, Owen J. T. McCarty, Joseph E. Aslan
Summary: Our study indicates that TKIs targeting Syk or BTK inhibit central platelet functional responses but may differentially affect protein activities and organization in critical systems downstream of Syk and BTK in platelets.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Chemistry, Medicinal
Xiaojing Chen, Lu Liu, Peng Liu, Yingying Chen, Dan Lin, Hao Yan, Qi Yan, Yi Wang, Yinda Qiu, Bo Fang, Huijing Huang, Jianchang Qian, Yunjie Zhao, Zhou Du, Qianwen Zhang, Xiaokun Li, Xiaohui Zheng, Zhiguo Liu
Summary: This study investigated the design, synthesis, and structure-activity relationships of novel pyrimidine-2,4-diamine derivatives that selectively inhibit PDGFR alpha/beta kinases. Compound 7m showed the most promising activity against PDGFR alpha and beta, with low IC50 values. It also exhibited significant cytotoxic effects against osteosarcoma cancer cell lines, as well as robust antitumor effects and low toxicity in a xenograft model. The compound demonstrated favorable pharmacokinetic properties and showed potential as a drug candidate for PDGFR-driven osteosarcoma.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jacquelyn R. Bedsaul, Neha Shah, Shelby M. Hutcherson, Joel L. Pomerantz
Summary: The CARD11 scaffold is responsible for controlling antigen receptor signaling, leading to the activation of NF-KB, JNK, and mTOR. Different types of germline mutations in CARD11 can cause Primary Immunodeficiency, with homozygous loss-of-function mutations causing CARD11 deficiency, heterozygous gain-of-function mutations causing BENTA disease, and heterozygous dominant-negative loss-of-function mutations causing CADINS. Through our study on loss-of-function CARD11 mutants, we identified that strong dominant negatives can disrupt signaling from mixed wild-type and mutant oligomers at the Opening Step and Cofactor Association Step in the CARD11 signaling cycle. These findings suggest that CARD11 oligomer subunits cooperate in at least two steps during antigen receptor signaling and shed light on how different loss-of-function mutations in the same oligomeric signaling hub can result in different inheritance patterns of disease.
Article
Genetics & Heredity
Xin Qi, Hongchang Gu, Lujiang Qu
Summary: This study investigated the inheritance patterns of alternative splicing in chickens through a reciprocal crossing experiment between White Leghorn and Cornish Game chicken breeds. Significant differences in alternative splicing events were observed between the two breeds in brain, muscle, and liver tissues, highlighting tissue and strain specificity. The study also revealed that a substantial portion of alternative splicing genes show conserved patterns in parental strains and hybrid crosses across all three tissues.
FRONTIERS IN GENETICS
(2021)
Review
Endocrinology & Metabolism
Panyisha Wu, Moya Zhang, Nicholas J. G. Webster
Summary: Alternative RNA splicing is an important biological process that has been linked to various clinical syndromes, but its applicability to common diseases is still uncertain. This review focuses on the changes in alternative RNA splicing in fatty liver disease and the role of splicing regulation in disease progression.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Clinical Neurology
Clara Y. B. Low, Jasinda H. Lee, Frances T. W. Lim, Chingli Lee, Clive Ballard, Paul T. Francis, Mitchell K. P. Lai, Michelle G. K. Tan
Summary: Studies have shown selective upregulation of FynT expression in the neocortex of patients with Alzheimer's disease, Parkinson's disease dementia, and dementia with Lewy bodies, which correlated with cognitive impairment, neuropathological lesions, soluble beta-amyloid, phosphorylated tau, and markers of microglia and astrocyte activation. This suggests that FynT may play a role in neurodegenerative dementias through effects on tauopathy and neuroinflammation.
Article
Biochemistry & Molecular Biology
Shinya Imada, Yoji Murata, Takenori Kotani, Masaki Hatano, Chunxiao Sun, Tasuku Konno, Jung-ha Park, Yasuaki Kitamura, Yasuyuki Saito, Hideki Ohdan, Takashi Matozaki
MOLECULAR AND CELLULAR BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Jung-ha Park, Takenori Kotani, Tasuku Konno, Jajar Setiawan, Yasuaki Kitamura, Shinya Imada, Yutaro Usui, Naoya Hatano, Masakazu Shinohara, Yasuyuki Saito, Yoji Murata, Takashi Matozaki
Article
Chemistry, Medicinal
Shingo Mori, Noriyasu Kamei, Yoji Murata, Kozo Takayama, Takashi Matozaki, Mariko Takeda-Morishita
JOURNAL OF PHARMACEUTICAL SCIENCES
(2017)
Article
Multidisciplinary Sciences
Yasuyuki Saito, Datu Respatika, Satomi Komori, Ken Washio, Taichi Nishimura, Takenori Kotani, Yoji Murata, Hideki Okazawa, Hiroshi Ohnishi, Yoriaki Kaneko, Katsuyuki Yui, Koji Yasutomo, Chikako Nishigori, Yoshihisa Nojima, Takashi Matozaki
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Biochemistry & Molecular Biology
Naoki Sawada, Takenori Kotani, Tasuku Konno, Jajar Setiawan, Yuka Nishigaito, Yasuyuki Saito, Yoji Murata, Ken-ichi Nibu, Takashi Matozaki
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Oncology
Yoji Murata, Daisuke Tanaka, Daisuke Hazama, Tadahiko Yanagita, Yasuyuki Saito, Takenori Kotani, Per-Arne Oldenborg, Takashi Matozaki
Review
Oncology
Yoji Murata, Yasuyuki Saito, Takenori Kotani, Takashi Matozaki
Article
Biochemistry & Molecular Biology
Chunxiao Sun, Yoji Murata, Shinya Imada, Tasuku Konno, Takenori Kotani, Yasuyuki Saito, Hideto Yamada, Takashi Matozaki
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Biology
Miho Sato-Hashimoto, Tomomi Nozu, Riho Toriba, Ayano Horikoshi, Miho Akaike, Kyoko Kawamoto, Ayaka Hirose, Yuriko Hayashi, Hiromi Nagai, Wakana Shimizu, Ayaka Saiki, Tatsuya Ishikawa, Ruwaida Elhanbly, Takenori Kotani, Yoji Murata, Yasuyuki Saito, Masae Naruse, Koji Shibasaki, Per-Arne Oldenborg, Steffen Jung, Takashi Matozaki, Yugo Fukazawa, Hiroshi Ohnishi
Article
Multidisciplinary Sciences
Tasuku Konno, Takenori Kotani, Ajar Setiawan, Yu Ka Nishigaito, Naoki Sawada, Shinya Imada, Yasuyuki Saito, Yoji Murata, Takashi Matozaki
Review
Oncology
Takashi Matozaki, Takenori Kotani, Yoji Murata, Yasuyuki Saito
Summary: The turnover of intestinal epithelial cells is regulated by various signaling pathways, including Wnt-beta-catenin and receptor protein tyrosine kinases. These pathways not only promote cell proliferation but also affect cell differentiation, showing cross-regulatory relationships with each other.
Editorial Material
Pharmacology & Pharmacy
Yoji Murata, Yasuyuki Saito, Takenori Kotani, Takashi Matozaki
EXPERT OPINION ON THERAPEUTIC TARGETS
(2020)
Article
Multidisciplinary Sciences
Mariko Sakamoto, Yoji Murata, Daisuke Tanaka, Yuka Kakuchi, Takeshi Okamoto, Daisuke Hazama, Yasuyuki Saito, Takenori Kotani, Hiroshi Ohnishi, Masayuki Miyasaka, Masato Fujisawa, Takashi Matozaki
Summary: Monotherapy with antibodies targeting SIRP alpha/SIRP beta 1 can induce antitumorigenic macrophages and inhibit tumor growth by promoting killing and phagocytosis of cancer cells by these macrophages. Therefore, SIRP beta 1 is a potential target for cancer immunotherapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Daisuke Hazama, Yizhen Yin, Yoji Murata, Makoto Matsuda, Takeshi Okamoto, Daisuke Tanaka, Naohiro Terasaka, Jinxuan Zhao, Mariko Sakamoto, Yuka Kakuchi, Yasuyuki Saito, Takenori Kotani, Yoshihiro Nishimura, Atsushi Nakagawa, Hiroaki Suga, Takashi Matozaki
CELL CHEMICAL BIOLOGY
(2020)
Article
Medicine, Research & Experimental
Tadahiko Yanagita, Yoji Murata, Daisuke Tanaka, Sei-ichiro Motegi, Eri Arai, Edwin Widyanto Daniwijaya, Daisuke Hazama, Ken Washio, Yasuyuki Saito, Takenori Kotani, Hiroshi Ohnishi, Per-Arne Oldenborg, Noel Verjan Garcia, Masayuki Miyasaka, Osamu Ishikawa, Yae Kanai, Takahide Komori, Takashi Matozaki