Article
Virology
Drayson Graves, Nikolas Akkerman, Scott Bachus, Peter Pelka
Summary: In this study, it was observed that 293 cells were not able to fully complement the late E1A transcripts, leading to growth defects in E1-deleted adenoviruses. This is likely due to splicing differences in E1A RNA between cells and infecting viruses. Complementation of late E1A mRNAs in 293 cells improved viral growth, highlighting the importance of protein complementation in virus production for applications such as vaccine development and gene therapy.
JOURNAL OF VIROLOGY
(2021)
Review
Chemistry, Medicinal
Ahmed K. ElHady, Dalia S. El-Gamil, Ashraf H. Abadi, Mohammad Abdel-Halim, Matthias Engel
Summary: Clk1 has been identified as a promising target for the treatment of various diseases, especially those related to deregulated alternative splicing. Clinical trials of small molecule inhibitors targeting Clk1 are underway for the treatment of solid cancer, which is promoted by oncogenic protein variants derived from alternative splicing. In addition, Clk1 has been implicated in the progression of Alzheimer's disease. However, most Clk1 inhibitors lack sufficient selectivity, affecting other Clk isoforms and Dyrk kinases.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Plant Sciences
Ibtissam Jabre, Saurabh Chaudhary, Wenbin Guo, Maria Kalyna, Anireddy S. N. Reddy, Weizhong Chen, Runxuan Zhang, Cornelia Wilson, Naeem H. Syed
Summary: Research suggests that nucleosome positioning affects cold-induced alternative splicing in plants. In Arabidopsis thaliana, different types of alternative splicing events are closely linked to characteristic nucleosome occupancy levels. Internal regions of protein-coding exons, known as exitrons, exhibit distinct nucleosome positioning patterns compared to other alternatively spliced regions.
Article
Biochemistry & Molecular Biology
Iga Dalidowska, Olga Gazi, Dorota Sulejczak, Maciej Przybylski, Pawel Bieganowski
Summary: The research showed that the Hsp90 inhibitor 17-AAG effectively reduces the replication rate of human adenovirus 5 and inhibits its transcription of early and late genes, viral DNA replication, and protein expression. Additionally, 17-AAG decreases the level of newly synthesized E1A protein, potentially explaining its anti-adenoviral activity by reducing E1A levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Ibtissam Jabre, Saurabh Chaudhary, Cornelia M. Wilson, Dorothee Staiger, Naeem Syed
Summary: Plants utilize gene regulatory mechanisms to adapt to environmental challenges. This study reveals that stochastic changes in DNA methylation can modulate nucleosome occupancy and alternative splicing (AS) in response to cold stress, thus influencing plant metabolism and stress adaptation.
Article
Plant Sciences
Tongtong Wang, Xiaofeng Wang, Haiyan Wang, Chao Yu, Chengyun Xiao, Yiwu Zhao, Huanan Han, Shuangshuang Zhao, Qun Shao, Jianhua Zhu, Yanxiu Zhao, Pingping Wang, Changle Ma
Summary: Alternative splicing of pre-mRNAs is crucial for plant growth and development. Serine/arginine-rich (SR) proteins are a conserved family of RNA-binding proteins that play a critical role in both constitutive and alternative splicing. However, the regulation of SR proteins' phosphorylation and its effect on gene transcription and alternative splicing during plant development remain poorly understood. In this study, we found that SRPKIIs in Arabidopsis specifically control the phosphorylation status of a subset of SR proteins, including SR45 and SC35, and regulate their subcellular localization.
Article
Biochemistry & Molecular Biology
Jamal Elhasnaoui, Giulio Ferrero, Valentina Miano, Lorenzo Franchitti, Isabella Tarulli, Lucia Coscujuela Tarrero, Santina Cutrupi, Michele De Bortoli
Summary: This study found that ESRP1 is overexpressed in breast cancer patients, particularly in luminal BCs, and is correlated with estrogen receptor alpha levels. Analysis of genome-binding profiles revealed that ER alpha regulates the expression of ESRP1 and ESRP2 genes. Knocking down ESRP1/2 led to dysregulation of 754 genes, including alterations in alternative splicing events involved in cell signaling, metabolism, cell growth, and EMT. Functional network analysis identified RAC1 as the hub node affected by ESRP1/2 silencing in ER alpha+ BCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Debanwita Roy Burman, Shalini Das, Chandrima Das, Rahul Bhattacharya
Summary: Enhanced metastasis and disease recurrence contribute to the high mortality rates in cancer. Epithelial-Mesenchymal Transition (EMT) and alternative splicing play crucial roles in cancer invasiveness, drug resistance, and stem-like behavior. Splicing factors control the splicing alterations of genes like FGFR and CD44 during trans-differentiation, impacting cancer progression.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Zerina Balic, Saurav Misra, Belinda Willard, Dieter P. Reinhardt, Suneel S. Apte, Dirk Hubmacher
Summary: ADAMTS proteases play important roles in the biosynthesis and breakdown of ECM molecules, with alternative splicing playing a significant role in regulating their proteolytic activity and cellular localization. This study characterizes the impact of alternative splicing on ADAMTS17, revealing two novel splice variants that affect protease activity through structural changes.
Article
Biochemistry & Molecular Biology
Kaiping Deng, Zhipeng Liu, Yalong Su, Zhen Zhang, Yixuan Fan, Yanli Zhang, Feng Wang
Summary: RUNX1T1 plays a crucial role in myogenesis by promoting cell proliferation, inhibiting myogenic differentiation and regulating alternative splicing events. Knockdown of RUNX1T1 leads to the impairment of myotube formation through the disruption of the calcium signaling pathway and altered expression levels of muscle-specific isoforms of ROCK2.
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)
Article
Biochemistry & Molecular Biology
Yasunori Akaike, Yuki Nakane, Taku Chibazakura
Summary: The adenoviral protein E1A, particularly the 13S variant, plays a crucial role in enhancing CDK2 activity and promoting G2/M-phase arrest. The CR1, CR2, and CR3 domains of E1A contribute to binding to the Cyclin A-CDK2 complex and activation of CDK2.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Bin Liu, Yuanlin Sun, Yang Zhang, Yanpeng Xing, Jian Suo
Summary: DEK is a potential proto-oncogene highly expressed in gastric cancer (GC). This study analyzed the global transcription and alternative splicing profiles regulated by DEK in a human GC cell line. It revealed that DEK regulates the expression and alternative splicing of multiple cancer-related genes, indicating its role as a possible oncogene. These findings expand the importance and feasibility of DEK as a clinical therapeutic target for human malignancies including GC.
Article
Cell Biology
Riho Komuro, Yuka Honda, Motoaki Yanaizu, Masami Nagahama, Yoshihiro Kino
Summary: Genetic variations of CD33, specifically the rs12459419 polymorphism on exon 2, affect its alternative splicing and have been associated with the risk of Alzheimer's disease. The minor allele promotes skipping of exon 2, resulting in a shorter CD33 isoform lacking the ligand-binding domain and reduced suppressive signaling on microglial activity. HNRNPA1 was found to promote exon 2 skipping, but simultaneous knockdown of HNRNPA1, HNRNPA2B1, and HNRNPA3 increased exon 2 inclusion, suggesting functional redundancy among these proteins.
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
Biochemistry & Molecular Biology
Misako Tanaka, Hiroyuki Harada, Hiroshi Kimura
Summary: Carcinogenesis is often associated with alterations in histone modifications. This study investigated the levels of various histone modifications in different types of oral squamous cell carcinoma (OSCC) cell lines and found that a high level of H3K9me3 could be a marker of metastasis. Additionally, suppressing H3K9me3 through knockdown of SUV39H1 and SUV39H2 inhibited cell proliferation and migration, suggesting H3K9me3 as a potential therapeutic target for OSCC treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ksenia Kuznetsova, Noemie M. Chabot, Martino Ugolini, Edlyn Wu, Manan Lalit, Haruka Oda, Yuko Sato, Hiroshi Kimura, Florian Jug, Nadine L. Vastenhouw
Summary: The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells. Proteins of the transcriptional machinery come together to form these bodies, but the process is not well understood. In this study, two large, isolated, and long-lived transcription bodies in zebrafish embryos were studied to characterize the dynamics of transcription body formation. The clustering of transcription factors, particularly Nanog and Sox19b, play a crucial role in initiating transcription and organizing these bodies.
Article
Cell & Tissue Engineering
Hiroki Ozawa, Azusa Kambe, Kodai Hibi, Satoshi Murakami, Akira Oikawa, Tetsuya Handa, Katsunori Fujiki, Ryuichiro Nakato, Katsuhiko Shirahige, Hiroshi Kimura, Nobuaki Shiraki, Shoen Kume
Summary: Human induced pluripotent stem cells (iPSCs) require high levels of methionine (Met) for maintaining pluripotency. Met deprivation leads to decreased levels of intracellular S-adenosyl-methionine (SAM), triggering differentiation and apoptosis of undifferentiated cells. Short-term Met deprivation affects the pluripotency network through epigenetic modifications, specifically on histone H3 trimethylation at lysine 4 (H3K4me3). The transcription start site (TSS) region of genes involved in transforming growth factor beta pathway, cholesterol biosynthetic process, as well as key pluripotent genes NANOG and POU5F1, are specifically affected by Met deprivation. Upon differentiation, loss of H3K27me3 occurs in many endodermal genes, leading to their activation and switching from a bivalent to a monovalent state (H3K4me3).
Article
Chemistry, Multidisciplinary
Akihiro Kobayashi, Tsubasa Matsuzawa, Takamitsu Hosoya, Suguru Yoshida
Summary: The interrupted Pummerer reaction of alkynyl sulfoxides with phenols is reported, leading to the efficient synthesis of various benz[b]furans through the unexplored electrophilic activation of the electron-deficient alkynyl sulfinyl group. Utilizing readily available alkynes, thiosulfonates, and phenols, we successfully prepared functionalized benz[b]furans.
Article
Chemistry, Analytical
Junya Adachi, Haruka Oda, Toshiaki Fukushima, Beni Lestari, Hiroshi Kimura, Hiroka Sugai, Kentaro Shiraki, Rei Hamaguchi, Kohei Sato, Kazushi Kinbara
Summary: Cell-imaging methods with functional fluorescent probes are widely used for evaluating physical parameters in cellular microenvironments. In this study, we developed viscosity-responsive fluorescent probes that are not dependent on the twisted intramolecular charge transfer (TICT) process. These probes showed enhanced fluorescence as the viscosity increased, allowing specific visualization of dense organelles in living cells under washout-free conditions. This research provides a new direction for developing functional fluorescent probes targeting dense organelles.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zhouen Zhang, Takashi Niwa, Kenji Watanabe, Takamitsu Hosoya
Summary: In this study, a two-phase radiosynthetic method for the ipso-C-11-cyanation of aryl fluorides was developed, using nickel-mediated C-F bond activation. A practical protocol was established that does not require a glovebox, making it applicable for general PET centers. This method enabled the efficient synthesis of diverse [C-11]aryl nitriles, including pharmaceutical drugs. Stoichiometric reactions and theoretical studies demonstrated the significant promotion effect of lithium chloride on the oxidative addition, facilitating rapid C-11-cyanation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Takashi Niwa, Tsuyoshi Tahara, Charles E. Chase, Francis G. Fang, Takayoshi Nakaoka, Satsuki Irie, Emi Hayashinaka, Yasuhiro Wada, Hidefumi Mukai, Kenkichi Masutomi, Yasuyoshi Watanabe, Yilong Cui, Takamitsu Hosoya
Summary: This study reports the successful 11C-radiolabeling of eribulin, an approved anticancer drug, which enables the quantitative measurement of eribulin migration into tumor tissue. The optimized synthetic method provides a reproducible way to produce [35-11C]eribulin with high radiochemical purity and molar activity. PET imaging using mice shows specific accumulation of [35-11C]eribulin in tumors without significant metabolic changes.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Psychiatry
Manon Dubol, Jana Immenschuh, My Jonasson, Kayo Takahashi, Takashi Niwa, Takamitsu Hosoya, Sara Roslin, Johan Wikstrom, Gunnar Antoni, Yasuyoshi Watanabe, Mark Lubberink, Anat Biegon, Inger Sundstrom-Poromaa, Erika Comasco
Summary: The study investigated the availability of aromatase in healthy women before and after nicotine exposure. The findings suggest that nicotine acutely decreases aromatase availability in the thalamic area, indicating a potential mechanism mediating the effects of nicotine on human behavior.
COMPREHENSIVE PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Fumiaki Nakamura, Hiroshi Kimura, Nobuhiro Fusetani, Yoichi Nakao
Summary: Two previously unreported onnamide analogs, 2Z- and 6Z-onnamides A (1 and 2), were isolated from the marine sponge Theonella conica collected at Amami-Oshima Is., Kagoshima Prefecture, Japan. The structures of compounds 1 and 2 were determined by spectoral analysis. They exhibited structure-activity relationships in histone modifications and cytotoxicity against HeLa and P388 cells.
Correction
Cell Biology
Adam Karoutas, Witold Szymanski, Tobias Rausch, Sukanya Guhathakurta, Eva A. Rog-Zielinska, Remi Peyronnet, Janine Seyfferth, Hui-Ru Chen, Rebecca de Leeuw, Benjamin Herquel, Hiroshi Kimura, Gerhard Mittler, Peter Kohl, Ohad Medalia, Jan O. Korbel, Asifa Akhtar
NATURE CELL BIOLOGY
(2023)
Article
Chemistry, Organic
Shinya Tabata, Mai Minoshima, Akihiro Kobayashi, Takamitsu Hosoya, Suguru Yoshida
Summary: Migrative thioamination of aryne intermediates using o-iodoaryl triflates and sulfilimines leads to the formation of highly functionalized o-thioaminated diaryl sulfides. The ring expansion of cyclic sulfilimines enables the synthesis of eight- and nine-membered organosulfur compounds from dibenzothiophene- and thianthrene-type sulfilimines, respectively.
Article
Biology
Haruka Oda, Yuko Sato, Shigehiro A. Kawashima, Yusuke Fujiwara, Mate Palfy, Edlyn Wu, Nadine L. Vastenhouw, Motomu Kanai, Hiroshi Kimura
Summary: Filamentous actin (F-actin) in the cytoplasm plays a crucial role in cell regulation, and recent studies have discovered its association with various functions in the nucleus. By live imaging of zebrafish embryos, it was shown that F-actin accumulates in nuclei during the interphase and reaches a peak during the prophase. Even after the breakdown of the nuclear envelope, patches of F-actin remain near the condensing chromosomes. This accumulation of F-actin in the nucleus may contribute to proper mitotic progression in zebrafish embryos.
Article
Biochemistry & Molecular Biology
Hiroshi Ochiai, Hiroaki Ohishi, Yuko Sato, Hiroshi Kimura
Summary: Higher-order genomic structures and the formation of condensates around genes have been found to play important roles in regulating gene expression. Recent advancements in technology allow for the visualization of the dynamic spatiotemporal relationship between these structures and transcriptional activity in living cells.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Organic
Jumpei Taguchi, Takumi Okuyama, Satomi Tomita, Takashi Niwa, Takamitsu Hosoya
Summary: An efficient method for producing 3-triazenylarynes from ortho-iodoaryl triflate-type precursors has been developed. The resulting arynes exhibit high regioselectivity in reactions with various arynophiles due to the presence of the triazenyl group. The 3-triazenylaryne precursors can be used as intermediates for the synthesis of diverse multisubstituted aromatic compounds through the transformation of the remaining triazenyl group in the aryne adducts and triazenyl group-directed ortho-C-H functionalization.
Correction
Biochemical Research Methods
Tetsuya Handa, Akihito Harada, Kazumitsu Maehara, Shoko Sato, Masaru Nakao, Naoki Goto, Hitoshi Kurumizaka, Yasuyuki Ohkawa, Hiroshi Kimura