Article
Chemistry, Multidisciplinary
Katarzyna Debiec, Elzbieta Sochacka
Summary: An efficient method of ureido linkage formation was developed for the epimerization-free one-pot synthesis of protected hypermodified N-6-threonylcarbamoyladenosine and its 2-SMe analog. Starting from different protected adenosine derivatives, the corresponding 3'-O-phosphoramidite monomers were successfully obtained.
Article
Biochemistry & Molecular Biology
Marouane Libiad, Thierry Douki, Marc Fontecave, Mohamed Atta
Summary: Post-transcriptional modifications of tRNA nucleotide play a crucial role in determining their folding, structure, and function. We have discovered and characterized a novel modified base called 2-methylthio-methylenethio-N-6-(cis-4-hydroxyisopentenyl)adenosine, which is found at position 37 in specific tRNAs. Furthermore, we have identified the catalytic cycle of the tRNA-diiron monooxygenase, MiaE, in Salmonella typhimurium, which converts the known 2-methylthio-methylenethio-N-6-(isopentenyl)adenosine nucleoside into this newly identified modified adenosine.
Article
Chemistry, Multidisciplinary
Zhentian Fang, Ziang Lu, Shaoqing Han, Yuanyuan Zhou, Wei Yang, Xiaolian Zhang, Xiang Zhou
Summary: A new method called ReACT-seq is introduced to detect ms2i6A transcriptome-wide at single-base resolution, through chemoselective reactions between the methylthio group and oxaziridine group. This method demonstrates high accuracy and resolution, and reveals that the modification of ms2i6A is conservative and may not exist in other RNAs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Yu Pan, Tong-Meng Yan, Jing-Rong Wang, Zhi-Hong Jiang
Summary: The study demonstrates that changes in tRNA modifications, specifically the increase in 4-demethylwyosine and decrease in hydroxywybutosine, contribute to cancer cell resistance to taxol therapy. This resistance is associated with the downregulation of the TYW2 enzyme, suggesting a potential novel mechanism for overcoming taxol resistance in cancer treatment.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Cell Biology
Jiahui Luo, Tao Xu, Kai Sun
Summary: m6A modification plays a crucial role in regulating post-transcriptional expression of target genes and is associated with various inflammatory states, including autoimmunity, infection, metabolic disease, cancer, neurodegenerative diseases, heart diseases, and bone diseases. Despite the significant potential of m6A as a biomarker and therapeutic target for inflammatory diseases, systematic knowledge of the relationship between m6A modification and inflammation in human diseases remains unclear.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Yuhao Zhang, Xiuchao Geng, Jianglong Xu, Qiang Li, Liangchao Hao, Zhaomu Zeng, Menglin Xiao, Jia Song, Fulin Liu, Chuan Fang, Hong Wang
Summary: This study systematically characterized the N6-methyladenosine modification pattern of circular RNAs in glioblastoma, identifying potential roles of N6-methyladenosine-modified circRNAs in the development of GBM. Through comprehensive RNA methylation sequencing and bioinformatics analysis, key molecules associated with N6-methyladenosine-mediated GBM progression were identified for further investigation.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Eva Scholler, James Marks, Virginie Marchand, Astrid Bruckmann, Christopher A. Powell, Markus Reichold, Christian Daniel Mutti, Katja Dettmer, Regina Feederle, Stefan Huttelmaier, Mark Helm, Peter Oefner, Michal Minczuk, Yuri Motorin, Markus Hafner, Gunter Meister
Summary: The mitochondrial protein METTL8 plays a crucial role in facilitating m(3)C methylation on mt-tRNAs, impacting respiratory chain activity and pancreatic cancer development. This modification leads to optimal composition and function of the mitochondria respiratory chain, with implications for patient survival and cellular metabolism.
Article
Chemistry, Multidisciplinary
Yuru Wang, Zijie Zhang, Caraline Sepich-Poore, Lisheng Zhang, Yu Xiao, Chuan He
Summary: The study introduces a new method, LEAD-m(6)A-seq, which significantly improves the efficiency of locus-specific analysis of m(6)A modification by coupling it to next generation sequencing technology. This strategy allows for high-throughput validation and detection of m(6)A modification at selected sites, with high reproducibility in evaluating differential methylation levels.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Mateja Condic, Damian J. Ralser, Niklas Kluemper, Joerg Ellinger, Maryam Qureischi, Eva K. Egger, Glen Kristiansen, Alexander Mustea, Thore Thiesler
Summary: There is growing evidence for the important role of post-transcriptional RNA modifications in cancer development and progression. This study examined the expression levels of m6A writers, readers, and erasers in cervical cancer cohorts and found that high protein expression levels of certain factors were associated with shorter overall survival. m6A may serve as a promising prognostic biomarker and therapeutic target in cervical cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xiaoyue Zhang, Qiu Peng, Lujuan Wang
Summary: This article reviews the role of m(6)A modifications in viral replication and virus-host interactions with a focus on DNA and RNA viruses associated with human diseases. It provides important insights for the design of therapeutic targets for tumors associated with viral infections.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)
Review
Cell Biology
Yingfeng Su, Yasen Maimaitiyiming, Lingfang Wang, Xiaodong Cheng, Chih-Hung Hsu
Summary: Phase separation is driven by RNA as a scaffold for proteins/RNA, particularly through the modification of m(6)A, which changes RNA properties and interactions to modulate phase separation and regulate biological processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Xin Wang, Rui Ma, Xilin Zhang, Lian Cui, Yangfeng Ding, Weimin Shi, Chunyuan Guo, Yuling Shi
Summary: N-6-methyladenosine (m(6)A) and circular RNAs (circRNAs) are important players in eukaryotic RNA regulation, with critical roles in cellular and disease processes. Recent research has focused on exploring the crosstalk between m(6)A and circRNAs, with future research directions also being a topic of interest.
Review
Biochemistry & Molecular Biology
Jian Li, Fangjuan Wang, Yongkang Liu, Huaizhi Wang, Bing Ni
Summary: N-6-methyladenosine (m(6)A), the most abundant RNA modification in eukaryotes, plays a crucial role in pancreatic cancer and dysregulation of its regulatory factors can profoundly affect the disease progression. m(6)A may serve as potential early diagnostic and therapeutic targets for pancreatic cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Review
Cell Biology
Juanjuan Han, Hui Kong, Xueqiang Wang, Xin-an Zhang
Summary: This review summarizes the molecular regulatory mechanism of noncoding RNA (ncRNA) N6-methyladenosine (m6A) modification in musculoskeletal disorders (MSD). Numerous studies have confirmed the mutual regulation between m6A and ncRNAs, and ncRNA m6A modification plays an essential role in the pathophysiological process of MSD.
CELL PROLIFERATION
(2022)
Review
Biochemistry & Molecular Biology
Jun Tang, Shuyan Chen, Guifang Jia
Summary: N6-methyladenosine (m6A) is a common internal chemical modification in eukaryotic mRNA, that plays important roles in gene expression regulation. It is installed, removed, and recognized by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) respectively. Research on m6A in plants has expanded, revealing its vital roles in plant development, stress responses, and crop improvement. This review discusses recent developments in m6A research, including detection methods, distribution, regulatory proteins, and molecular and biological functions in plants, and provides perspectives for future investigations.
PLANT COMMUNICATIONS
(2023)
Review
Cell Biology
Tsutomu Suzuki
Summary: tRNAs undergo heavy post-transcriptional modifications, which play crucial roles in accurate codon recognition and reading frame maintenance during protein synthesis. Recent studies have shown that tRNA modifications can be dynamically altered in response to cellular and environmental stresses, and deficiencies in tRNA modification can lead to mitochondrial diseases, neurological disorders, and cancer.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Y. Nagayoshi, T. Chujo, S. Hirata, H. Nakatsuka, C-W Chen, M. Takakura, K. Miyauchi, Y. Ikeuchi, B. C. Carlyle, R. R. Kitchen, T. Suzuki, F. Katsuoka, M. Yamamoto, Y. Goto, M. Tanaka, K. Natsume, A. C. Nairn, K. Tomizawa, F-Y Wei
Summary: Ftsj1 gene is implicated in X-linked intellectual disability, responsible for 2'-O-methylation of cytosolic tRNAs; Knockout of Ftsj1 leads to slow decoding and reduced translation efficiency, resulting in abnormal synaptic function; The study highlights the essential role of tRNA modification in the brain and provides mechanistic insights into FTSJ1-related XLID.
Article
Biochemistry & Molecular Biology
Kensuke Ninomiya, Junichi Iwakiri, Mahmoud Khamis Aly, Yuriko Sakaguchi, Shungo Adachi, Tohru Natsume, Goro Terai, Kiyoshi Asai, Tsutomu Suzuki, Tetsuro Hirose
Summary: The study reveals the role of nuclear stress bodies in repressing RNA splicing during stress recovery through two distinct mechanisms involving protein sequestration and N-6-methyladenosine modification. The sequestration of m(6)A writer complex by nSBs leads to the inhibition of m(6)A-dependent splicing, highlighting the importance of nSBs in regulating temperature-dependent splicing.
Article
Biochemistry & Molecular Biology
Eichi Watabe, Marina Togo-Ohno, Yuma Ishigami, Shotaro Wani, Keiko Hirota, Mariko Kimura-Asami, Sharmin Hasan, Satomi Takei, Akiyoshi Fukamizu, Yutaka Suzuki, Tsutomu Suzuki, Hidehito Kuroyanagi
Summary: The homeostasis of SAM synthetase in C. elegans is maintained through alternative splicing regulation and m(6)A modification, with splicing regulation achieved through NMD and regulated by U6 snRNA methyltransferase.
Article
Multidisciplinary Sciences
Yuma Ishigami, Takayuki Ohira, Yui Isokawa, Yutaka Suzuki, Tsutomu Suzuki
Summary: The modification of N-6-methyladenosine on spliceosomal U6 snRNA facilitates efficient recognition of the splice sites through cooperation with U5 snRNA, allowing for variation in the 5' exon sequence and contributing to protein sequence diversity.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Katarzyna Frankowska, Elzbieta Sochacka
Summary: A novel and efficient method for synthesizing N-6-hydantoin-modified adenosines has been developed. The method utilizes readily available adenosine derivatives and involves a series of reactions to obtain the desired products.
Article
Biochemistry & Molecular Biology
Jing Wang, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
Summary: CdiA-CTEC869 cleaves specific tRNAs by interacting with translation factors Tu and Ts, and interacts with domain II of Tu to affect the structure and cleavage efficiency of tRNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Yuta Noda, Shunpei Okada, Tsutomu Suzuki
Summary: Stop codon recoding is a mechanism that regulates selenoprotein expression during skeletal muscle differentiation by modulating A-to-I RNA editing and stop codon recoding. It plays a crucial role in maintaining redox homeostasis during myoblast differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Kulik, Klaudia Sadowska, Ewelina Wielgus, Barbara Pacholczyk-Sienicka, Elzbieta Sochacka, Barbara Nawrot
Summary: The 2-selenouridine component of tRNA is more susceptible to oxidation and exhibits antioxidant potential in cells. Additionally, new oligomeric nucleosides are formed during the oxidation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Luciano G. Dolce, Aubree A. Zimmer, Laura Tengo, Felix Weis, Mary Anne T. Rubio, Juan D. Alfonzo, Eva Kowalinski
Summary: The study reveals how the eukaryotic ADAT2/3 deaminase selects its substrates and binds to tRNA through sequence-independent flexible or intrinsically unfolded motifs, and identifies a gating mechanism for substrate entry to the active site.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ena Tomoda, Asuteka Nagao, Yuki Shirai, Kana Asano, Takeo Suzuki, Brendan J. Battersby, Tsutomu Suzuki
Summary: Mutations in mitochondrial tRNA genes can lead to mitochondrial dysfunction. The diseases MELAS and MERRF are caused by pathogenic point mutations in mtDNA's tRNA genes. The modified tRNAs fail to efficiently decode codons, resulting in defective translation of respiratory chain proteins in mitochondria. Restoring the modified tRNAs can activate mitochondrial function in patient cells and pave the way for epitranscriptomic therapies for mitochondrial diseases.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Saori Ueda, Mikako Yagi, Ena Tomoda, Shinya Matsumoto, Yasushi Ueyanagi, Yura Do, Daiki Setoyama, Yuichi Matsushima, Asuteka Nagao, Tsutomu Suzuki, Tomomi Ide, Yusuke Mori, Noriko Oyama, Dongchon Kang, Takeshi Uchiumi
Summary: This study identified a novel mutation (3290T > C) that improved mitochondrial dysfunction caused by the 3243A > G mutation in mitochondrial diseases. The findings provide a potential therapeutic strategy for diseases associated with pathogenic mutations in mitochondrial tRNAs.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Karolina Podskoczyj, Katarzyna Kulik, Joanna Wasko, Barbara Nawrot, Tsutomu Suzuki, Grazyna Leszczynska
Summary: A single point mutation in the human mitochondrial tRNA(Met) gene causes severe mitochondrial disorders associated with hypertension, type 2 diabetes and LHON. This mutation leads to the exchange of A(37) in the anticodon loop of hmt-tRNA(Met) for G(37) and 1-methylguanosine. The first synthesis and structural/biophysical studies of the anticodon stem and loop of pathogenic hmt-tRNAs(Met) are presented here.
CHEMICAL COMMUNICATIONS
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
M. Sierant, R. Szewczyk, K. Krolewska-Golinska, A. Dziergowska, P. Bernat, E. Sochacka, B. Nawrot
Article
Chemistry, Multidisciplinary
Katarzyna Debiec, Elzbieta Sochacka
Summary: An efficient method of ureido linkage formation was developed for the epimerization-free one-pot synthesis of protected hypermodified N-6-threonylcarbamoyladenosine and its 2-SMe analog. Starting from different protected adenosine derivatives, the corresponding 3'-O-phosphoramidite monomers were successfully obtained.
