Article
Cell & Tissue Engineering
Feng Zhang, Kijun Yoon, Daniel Y. Zhang, Nam-Shik Kim, Guo-li Ming, Hongjun Song
Summary: Increasing evidence supports the crucial roles of METTL8 and mitochondrial tRNA modification in maintaining embryonic cortical neural stem cells in mice and humans. Deletion of METTL8 leads to reduced mitochondrial protein synthesis and attenuated respiration, resulting in impaired neural stem cell maintenance. These findings highlight the conserved epitranscriptomic mechanism of METTL8 in regulating mitochondrial function and neural stem cell homeostasis.
Article
Biochemistry & Molecular Biology
Meng-Han Huang, Gui-Xin Peng, Xue-Ling Mao, Jin-Tao Wang, Jing-Bo Zhou, Jian-Hui Zhang, Meirong Chen, En-Duo Wang, Xiao-Long Zhou
Summary: The study identified different isoforms of METTL8 that play various roles in different cell compartments. The isoforms have distinct localization and show different mechanisms in the modification of mitochondrial tRNA. The interaction between SARS2 and METTL8-Iso1 was found to enhance the modification activity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Caley A. Hogan, Scott J. Gratz, Jennifer L. Dumouchel, Rajan S. Thakur, Ambar Delgado, Jenna M. Lentini, Kimberly R. Madhwani, Dragony Fu, Kate M. O'Connor-Giles
Summary: TRMT9B is identified as a new regulator of synapse formation and function in Drosophila, specifically enriched in the nervous system. It acts postsynaptically to regulate synaptogenesis and promote neurotransmission, possibly through its methyltransferase function.
Article
Chemistry, Multidisciplinary
Yi Hao, Xiang Li, Ke Qin, Yujie Shi, Yanwen He, Che Zhang, Bo Cheng, Xiwen Zhang, Guangyu Hu, Shuyu Liang, Qi Tang, Xing Chen
Summary: The O-GlcNAc modification is found to affect the self-renewal and differentiation of embryonic stem cells (ESCs), and the core pluripotency transcription factor NANOG is regulated by this modification. During neuronal lineage differentiation, the O-GlcNAc modification decreases, and suppressing O-GlcNAcylation can upregulate neuron-related genes, thus influencing the fate determination of ESCs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Andy Chan, Sophia Ma, Bret J. Pearson, Danny Chan
Summary: The extracellular matrix plays a crucial role in the maintenance, regeneration, and differentiation of stem cells within their niche. By studying the collagen gene family in the freshwater planarian Schmidtea mediterranea, researchers have identified a key gene, col4-1, which influences the proliferation of neoblasts. Furthermore, evidence suggests that an interaction between type IV collagen, the discoidin domain receptor, and neuregulin-7 regulate the balance of symmetric and asymmetric division of neoblasts through the NRG-7/EGFR pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Yunquan He, Jieyu Guo, Yueyang Yu, Jiayu Jin, Qingjun Jiang, Qinhan Li, Siyu Ma, Qi Pan, Jiayi Lin, Nan Jiang, Jinghua Ma, Yongbo Li, Yannan Hou, Xiuling Zhi, Lindi Jiang, Lefeng Qu, Elena Osto, Xinhong Wang, Xiangxiang Wei, Dan Meng
Summary: The role of BACH1 in the differentiation of VSMCs from hESCs has been investigated. The study found that BACH1 facilitates the expression of VSMC marker genes by binding to CARM1, leading to the in vitro differentiation of hESCs into VSMCs.
Article
Multidisciplinary Sciences
Seohyun Kima, Jin-Sup Park, Jaehoon Lee, Kiseok Keith Lee, Ok-Sun Park, Hee-Seung Choi, Pil Joon Seo, Hyung-Taeg Cho, Jennifer M. Frost, Robert L. Fischer, Yeonhee Choi, Masaru Ohme-Takagi
Summary: The DEMETER (DME) DNA demethylase plays a crucial role in the sporophytic growth and development in Arabidopsis, influencing various aspects of plant growth and development by altering specific gene expression pathways. Its activity affects the transcriptome of developing Arabidopsis plants and may be involved in maintaining stem cell activities during the sporophytic life cycle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Andrea Berardi, Oronza A. Botrugno, Giacomo Quilici, Jose Manuel Garcia Manteiga, Angela Bachi, Giovanni Tonon, Giovanna Musco
Summary: NSD1, NSD2, and NSD3 proteins belong to a family of histone 3 lysine 36 (H3K36) methyltransferases with similar domain architecture. However, their activities differ due to variations in their non-enzymatic domains and their ability to recognize different epigenetic marks and interactors. In this study, the researchers provide structural evidence for the distinctiveness of the PHDvC5HCH domain of NSD1 in recognizing the C2HR Zinc finger domain of Nizp1. They also demonstrate the functional association between Nizp1 and NSD1 in driving the unscheduled expression of certain genes in leukemia. These findings shed light on the pathophysiological relevance of the Nizp1-NSD1 interaction and suggest it as a potential therapeutic target for inhibiting oncogenic properties.
Article
Multidisciplinary Sciences
Emilie Brule, Ying Wang, Yining Li, Yeu-Farn Lin, Xiang Zhou, Luisina Ongaro, Carlos A. Alonso, Evan R. S. Buddle, Alan L. Schneyer, Chang-Hyeock Byeon, Cynthia S. Hinck, Natalia Mendelev, John P. Russell, Mitra Cowan, Ulrich Boehm, Frederique Ruf-Zamojski, Michel Zamojski, Cynthia L. Andoniadou, Stuart C. Sealfon, Craig A. Harrison, Kelly L. Walton, Andrew P. Hinck, Daniel J. Bernard
Summary: The study reveals TGFBR3L as the co-receptor for inhibin B, playing a crucial role in regulating FSH levels and ovarian follicle development. TGFBR3L has specific binding ability to inhibin B, with its knockdown or overexpression affecting inhibin B activity.
Article
Cell Biology
Isao Masuda, Yuka Yamaki, Rajesh Detroja, Somnath Tagore, Henry Moore, Sunita Maharjan, Yuko Nakano, Thomas Christian, Ryuma Matsubara, Todd M. Lowe, Milana Frenkel-Morgenstern, Ya -Ming Hou
Summary: This study demonstrates the impact of m(1)G37 on resolving codon usage bias and its role in cell viability. Results show that m(1)G37 plays a crucial role in neutralizing differential translation of proline codons.
Article
Multidisciplinary Sciences
Pengfei Guo, Nam Hoang, Joseph Sanchez, Elaine H. Zhang, Keshari Rajawasam, Kristiana Trinidad, Hong Sun, Hui Zhang
Summary: The authors demonstrate that the assembly/disassembly of mammalian SWI/SNF complexes is dynamically regulated by a lysine methylation mechanism involving LSD1 demethylase and L3MBTL3 methyl-lysine reader protein. This mechanism targets SET7-methylated lysines in SMARCC1 and SMARCC2 for proteolysis by CRL4 ubiquitin ligase. The study also reveals the critical role of LSD1 and L3MBTL3 in maintaining the pluripotency and self-renewal of embryonic stem cells, as well as regulating proteolysis induced by loss of SWI/SNF subunits.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Tian Xia, Ming Liu, Quan Zhao, Jian Ouyang, Bing Chen, Peipei Xu
Summary: PRMT5 is upregulated in multiple myeloma, and its inhibition enhances cell pyroptosis, while the expression of CASP1 negatively correlated with PRMT5 can be restored by suppressing PRMT5, promoting cell pyroptosis in MM.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Sue Yu, Jia Li, Guanxu Ji, Zhen Long Ng, Jiamin Siew, Wan Ning Lo, Ying Ye, Yuan Yuan Chew, Yun Chau Long, Wensheng Zhang, Ernesto Guccione, Yuin Han Loh, Zhi-Hong Jiang, Henry Yang, Qiang Wu
Summary: Chromatin modification is crucial for pluripotency maintenance in embryonic stem cells. Npac, a reader of H3K36me3, is essential for the transcriptional elongation of pluripotency genes by interacting with RNA Pol II and positive transcription elongation factor b.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2022)
Article
Multidisciplinary Sciences
Guanxu Ji, Xiaoxiao Xiao, Min Huang, Qiang Wu
Summary: Jmjd6 is a nuclear protein that plays a critical role in cell differentiation and embryo development. However, its function in mammalian ES cell identity and reprogramming has been unclear. This study demonstrates that depletion of Jmjd6 leads to downregulation of pluripotency genes and affects apoptosis, glycolysis, cell cycle, and protein hydroxylation. Additionally, Jmjd6 depletion reduces BrdU incorporation in cells. Overexpression of Jmjd6 enhances the reprogramming efficiency of MEFs, while depletion of Jmjd6 reduces the efficiency.
Article
Multidisciplinary Sciences
Hideki Furuya, Yuka Sasaki, Runpu Chen, Rafael Peres, Kanani Hokutan, Kaoru Murakami, Nari Kim, Owen T. M. Chan, Ian Pagano, Lars Dyrskjot, Jorgen B. Jensen, Per-Uno Malmstrom, Ulrika Segersten, Yijun Sun, Abolfazl Arab, Hani Goodarzi, Steve Goodison, Charles J. Rosser
Summary: The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, but recent studies have revealed its role in promoting human cancers by regulating angiogenesis and tumor cell survival. This study found that PAI-1 expression levels correlated with tumor grade, stage, and overall survival in bladder cancer. Further investigation showed that nuclear PAI-1 can influence gene expression programs and support malignancy.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Grace Png, Raffaele Gerlini, Konstantinos Hatzikotoulas, Andrei Barysenka, N. William Rayner, Lucija Klaric, Birgit Rathkolb, Juan A. Aguilar-Pimentel, Jan Rozman, Helmut Fuchs, Valerie Gailus-Durner, Emmanouil Tsafantakis, Maria Karaleftheri, George Dedoussis, Claus Pietrzik, James F. Wilson, Martin Hrabe Angelis, Christoph Becker-Pauly, Arthur Gilly, Eleftheria Zeggini
Summary: In this study, a protein quantitative trait locus (pQTL) analysis was performed on two Greek cohorts, identifying 301 independently associated pQTL variants for 170 proteins related to cardiometabolic processes. The study also discovered rare variants and observed changes in frequency of certain pQTL variants in the isolated populations. Additionally, the study identified proteins causally associated with cardiometabolic traits and described a knock-out Mep1b mouse model.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Lillian Garrett, Dietrich Truembach, Nadine Spielmann, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe De Angelis, Sabine M. Hoelter
Summary: Neuropsychiatric diseases represent a significant global disease burden and require innovative approaches for pathogenic understanding, biomarker identification, and therapeutic strategies. The malfunction of the heart/brain axis, particularly through the autonomic nervous system and brain central autonomic network interaction, plays a crucial role in the etiology of these diseases. This inter-relationship offers potential avenues for novel diagnosis and treatment approaches.
Article
Biochemistry & Molecular Biology
Nadine Spielmann, Christina Schenkl, Timea Komlodi, Patricia da Silva-Buttkus, Estelle Heyne, Jana Rohde, Oana Amarie, Birgit Rathkolb, Erich Gnaiger, Torsten Doenst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Marten Szibor
Summary: Deletion of the Uqcrh gene causes abnormalities in cardiac morphology and contractility in mice, but does not increase the production of mitochondrial reactive oxygen species. This study provides important information for understanding rare mitochondrial disorders.
Article
Genetics & Heredity
Long Guo, Smrithi Salian, Jing-yi Xue, Nicola Rath, Justine Rousseau, Hyunyun Kim, Sophie Ehresmann, Shahida Moosa, Norio Nakagawa, Hiroshi Kuroda, Jill Clayton-Smith, Juan Wang, Zheng Wang, Siddharth Banka, Adam Jackson, Yan-min Zhang, Zhen-jie Wei, Irina Huening, Theresa Brunet, Hirofumi Ohashi, Molly F. Thomas, Caleb Bupp, Noriko Miyake, Naomichi Matsumoto, Roberto Mendoza-Londono, Gregory Costain, Gabriele Hahn, Nataliya Di Donato, Goekhan Yigit, Takahiro Yamada, Gen Nishimura, K. Mark Ansel, Bernd Wollnik, Martin Hrabe de Angelis, Andre Megarbane, Jill A. Rosenfeld, Vigo Heissmeyer, Shiro Ikegawa, Philippe M. Campeau
Summary: ERI1 is a 30-to-50 exoribonuclease involved in RNA metabolic pathways. Bi-allelic ERI1 variants are associated with a phenotypic dichotomy, causing a severe spondyloepimetaphyseal dysplasia in some individuals with missense variants, while individuals with null variants show mild intellectual disability and digital anomalies. The missense variants lead to a loss of exoribonuclease activity, resulting in defective 5.8S rRNA processing and decreased degradation of histone mRNAs. This study establishes the importance of ERI1-mediated RNA metabolism in human skeletal patterning and chondrogenesis.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Endocrinology & Metabolism
Simon I. I. Dreher, Martin Irmler, Olga Pivovarova-Ramich, Katharina Kessler, Karsten Juerchott, Carsten Sticht, Louise Fritsche, Patrick Schneeweiss, Juergen Machann, Andreas F. H. Pfeiffer, Martin Hrabe de Angelis, Johannes Beckers, Andreas L. L. Birkenfeld, Andreas Peter, Andreas M. M. Niess, Cora Weigert, Anja Moller
Summary: This study examined the response of subcutaneous adipose tissue (SAT) to exercise and compared it with skeletal muscle. The results showed that SAT responds differently to exercise, with reductions in transcripts related to lipid storage and lipogenesis, as well as modulation of the circadian rhythm, which can potentially prevent metabolic syndrome progression towards diabetes.
INTERNATIONAL JOURNAL OF OBESITY
(2023)
Article
Biology
Esther Stroo, Leen Janssen, Olga Sin, Wytse Hogewerf, Mirjam Koster, Liesbeth Harkema, Sameh A. Youssef, Natalie Beschorner, Anouk H. G. Wolters, Bjorn Bakker, Lore Becker, Lilian Garrett, Susan Marschall, Sabine M. Hoelter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Amanth Thathiah, Floris Foijer, Bart van de Sluis, Jan van Deursen, Matthias Jucker, Alain de Brun, Ellen A. A. Nollen
Summary: In age-related neurodegenerative diseases, disease-specific proteins form amyloid-like deposits. Depletion of SERF proteins can ameliorate this process. However, it is unknown whether SERF modifies amyloid pathology in mammalian brain.
LIFE SCIENCE ALLIANCE
(2023)
Article
Cell Biology
Daniel Garger, Martin Meinel, Tamina Dietl, Christina Hillig, Natalie Garzorz-Stark, Kilian Eyerich, Martin Hrabe de Angelis, Stefanie Eyerich, Michael P. P. Menden
Summary: Through studying the association between various phenotypic traits and lifespan, it was found that somatic mutation and resting heart rate are negatively correlated with lifespan, while other traits show strong associations. Resting heart rate enhances the prediction of lifespan, indicating its direct influence or representation of lower-level mechanisms associated with lifespan.
Article
Genetics & Heredity
Daniel G. Calame, Tianyu Guo, Chen Wang, Lillian Garrett, Angad Jolly, Moez Dawood, Alina Kurolap, Noa Zunz Henig, Jawid M. Fatih, Isabella Herman, Haowei Du, Tadahiro Mitani, Lore Becker, Birgit Rathkolb, Raffaele Gerlini, Claudia Seisenberger, Susan Marschall, Jill Hunter, Amanda Gerard, Alexis Heidlebaugh, Thomas Challman, Rebecca C. Spillmann, Shalini N. Jhangiani, Zeynep Coban-Akdemir, Seema Lalani, Lingxiao Liu, Anya Revah-Politi, Alejandro Iglesias, Edwin Guzman, Evan Baugh, Nathalie Boddaert, Sophie Rondeau, Clothide Ormieres, Giulia Barcia, Queenie K. G. Tan, Sophie Isabelle Thiffault, Tomi Pastinen, Kazim Sheikh, Suur Biliciler, Davide Mei, Federico Melani, Vandana Shashi, Yuval Yaron, Mary Steele, Emma Wakeling, Elsebet Ostergaard, Francisca Undiagnosed Dis Network, Francisca Millan, Teresa Santiago-Sim, Julien Thevenon, Ange-Line Bruel, Christel Thauvin-Robinet, Denny Popp, Konrad Platzer, Pawel Gawlinski, Wojciech Wiszniewski, Dana Marafi, Davut Pehlivan, Jennifer E. Posey, Richard A. Gibbs, Valerie Gailus-Durner, Renzo Guerrini, Helmut Fuchs, Martin Hrabe de Angelis, Sabine M. Hoelter, Hoi-Hung Cheung, Shen Gu, James R. Lupski
Summary: DExD/H-box RNA helicases (DDX/DHX) are part of a large gene family that encodes enzymes and variations in these genes can lead to neurodevelopmental disorders and cancer. By analyzing genetic data, researchers found rare variants in the DHX9 gene in individuals with different disorders ranging from neurodevelopmental disorders to a specific type of polyneuropathy. Further experiments confirmed that DHX9 is important for neurodevelopment and neuronal homeostasis.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Cell Biology
Jennifer Maurer, Xinjie Zhao, Martin Irmler, Anders Gudiksen, Nanna S. Pilmark, Qi Li, Thomas Goj, Johannes Beckers, Martin Hrabe de Angelis, Andreas L. Birkenfeld, Andreas Peter, Rainer Lehmann, Henriette Pilegaard, Kristian Karstoft, Guowang Xu, Cora Weigert
Summary: Metformin treatment leads to lactate production and secretion, as well as reduced glucose consumption. It inhibits respiratory chain complex I and alters cellular redox state, decreasing pyruvate oxidation. These findings suggest that metformin induces dose-dependent lactate production in skeletal muscle by shifting the equilibrium of lactate dehydrogenase reaction.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Howard T. Jacobs, Marten Szibor, Birgit Rathkolb, Patricia da Silva-Buttkus, Juan Antonio Aguilar-Pimentel, Oana V. Amarie, Lore Becker, Julia Calzada-Wack, Nathalia Dragano, Lillian Garrett, Raffaele Gerlini, Sabine M. Hoelter, Tanja Klein-Rodewald, Markus Kraiger, Stefanie Leuchtenberger, Susan Marschall, Manuela A. Oestereicher, Kristina Pfannes, Adrian Sanz-Moreno, Claudia Seisenberger, Nadine Spielmann, Claudia Stoeger, Wolfgang Wurst, Helmut Fuchs, Martin Hrabe de Angelis, Valerie Gailus-Durner
Summary: The alternative oxidase (AOX) can delay the onset and progression of respiratory-chain diseases, but it does not provide long-term benefit.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Marie Lucienne, Raffaele Gerlini, Birgit Rathkolb, Julia Calzada-Wack, Patrick Forny, Stephan Wueest, Andres Kaech, Florian Traversi, Merima Forny, Celine Burer, Antonio Aguilar-Pimentel, Martin Irmler, Johannes Beckers, Sven Sauer, Stefan Koelker, Joseph P. Dewulf, Guido T. Bommer, Daniel Hoces, Valerie Gailus-Durner, Helmut Fuchs, Jan Rozman, D. Sean Froese, Matthias R. Baumgartner, Martin Hrabe de Angelis
Summary: Inherited disorders of mitochondrial metabolism, such as isolated methylmalonic aciduria, disrupt energy-producing pathways and pose challenges to energetic homeostasis. The study on a mouse model of methylmalonyl-CoA mutase (Mmut)-type methylmalonic aciduria revealed reduced appetite, energy expenditure, body mass, and altered adipose tissue functioning. The findings provide insights into energy imbalance in methylmalonic aciduria and have implications for disease understanding and patient management.
HUMAN MOLECULAR GENETICS
(2023)
Article
Endocrinology & Metabolism
Arvid Sandforth, Reiner Jumpertz von Schwartzenberg, Elsa Vazquez Arreola, Robert L. Hanson, Gencer Sancar, Sarah Katzenstein, Karl Lange, Hubert Preissl, Simon Dreher, Cora Weigert, Robert Wagner, Kostantinos Kantartzis, Fritz Schick, Rainer Lehmann, Andreas Peter, Nikoletta Katsouli, Vasilis Ntziachristos, Corinna Dannecker, Louise Fritsche, Nikolaos Perakakis, Martin Heni, Peter Paul Nawroth, Stefan Kopf, Andreas F. H. Pfeiffer, Stefan Kabisch, Michael Stumvoll, Peter E. H. Schwarz, Hans Hauner, Andreas Lechner, Jochen Seissler, Iryna Yurchenko, Andrea Icks, Michele Solimena, Hans-Ulrich Haering, Julia Szendroedi, Annette Schuermann, Martin Hrabe de Angelis, Matthias Blueher, Michael Roden, Stefan R. Bornstein, Norbert Stefan, Andreas Fritcher, Andreas Birkenfeld
Summary: This study investigates the mechanisms of weight loss-induced remission in people with prediabetes. The results suggest that weight loss can improve insulin sensitivity, reduce visceral adipose tissue, and lower the risk of developing type 2 diabetes. The authors propose that remission of prediabetes should be the primary therapeutic aim.
LANCET DIABETES & ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Meriem Ouni, Fabian Eichelmann, Markus Jaehnert, Christin Krause, Sophie Saussenthaler, Christiane Ott, Pascal Gottmann, Thilo Speckmann, Peter Huypens, Stefan Wolter, Oliver Mann, Martin Hrabe De Angelis, Johannes Beckers, Henriette Kirchner, Matthias B. Schulze, Annette Schuermann
Summary: Better disease management can be achieved by identifying novel epigenetic biomarkers that determine the risk of type 2 diabetes (T2D) at an early stage. This study found that differences in gene expression and DNA methylation in the liver could be used as potential biomarkers for T2D. The downregulation of the HAMP gene, associated with elevated DNA methylation, was identified as a potential early marker for T2D.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Bachuki Shashikadze, Libera Valla, Salvo Danilo Lombardo, Cornelia Prehn, Mark Haid, Fabien Riols, Jan Bernd Stoeckl, Radwa Elkhateib, Simone Renner, Birgit Rathkolb, Joerg Menche, Martin Hrabe de Angelis, Eckhard Wolf, Elisabeth Kemter, Thomas Froehlich
Summary: This study investigates the effects of maternal hyperglycemia on the liver of neonates using multi-omics analysis. The findings suggest that maternal hyperglycemia can lead to lipid accumulation and abnormal choline metabolism in the liver of newborns.
MOLECULAR METABOLISM
(2023)
Meeting Abstract
Endocrinology & Metabolism
R. Jumpertz von Schwartzenberg, K. Bodis, J. Martin, M. Schon, M. Hrabe de Angelis, N. Perakakis, S. Kabisch, A. Pfeiffer, M. Blueher, J. Szendroedi, N. Stefan, R. Wagner, A. L. Birkenfeld, M. Roden, A. Fritsche