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A DNA phosphorothioation pathway via adenylated intermediate modulates Tdp machinery.
Nat Chem Biol
January 2025
Department of Gastroenterology, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
In prokaryotes, the non-bridging oxygen in the DNA sugar-phosphate backbone can be enzymatically replaced by a sulfur atom, resulting in phosphorothioate (PT) modification. However, the mechanism underlying the oxygen-to-sulfur substitution remains enigmatic. In this study, we discovered a hypercompact DNA phosphorothioation system, TdpABC, in extreme thermophiles.
View Article and Find Full Text PDFCharacterization of acidic lysine acylations in mycobacteria.
Front Microbiol
December 2024
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Article Synopsis
- Protein acetylation is a widely studied post-translational modification, and recent research has identified three new forms: lysine malonylation, succinylation, and glutarylation, which mainly affect energy metabolism in diseases caused by Mycobacterium pathogens.
- Methods involved using high-affinity antibody enrichment and LC-MS/MS analysis to characterize these new lysine modifications and assess their functional impacts in certain proteins.
- Results showed significant global substrate characterization for these acylations, revealing connections to ribosomal function and various metabolic pathways, highlighting their importance in cellular processes.
The biogenesis and regulation of animal microRNAs.
Nat Rev Mol Cell Biol
December 2024
Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.
MicroRNAs (miRNAs) are small, yet profoundly influential, non-coding RNAs that base-pair with mRNAs to induce RNA silencing. Although the basic principles of miRNA biogenesis and function have been established, recent breakthroughs have yielded important new insights into the molecular mechanisms of miRNA biogenesis. In this Review, we discuss the metazoan miRNA biogenesis pathway step-by-step, focusing on the key biogenesis machinery, including the Drosha-DGCR8 complex (Microprocessor), exportin-5, Dicer and Argonaute.
View Article and Find Full Text PDFStructural basis for aminoacylation of cellular modified tRNA by human lysyl-tRNA synthetase.
bioRxiv
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven CT, 06511, USA.
The average eukaryotic tRNA contains 13 posttranscriptional modifications; however, their functional impact is largely unknown. Our understanding of the complex tRNA aminoacylation machinery in metazoans also remains limited. Herein, using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we provide the mechanistic basis for recognition and aminoacylation of fully-modified cellular tRNA by human lysyl-tRNA synthetase (h-LysRS).
View Article and Find Full Text PDFVarious metabolic abnormalities, including obesity, insulin resistance, hypertension, dyslipidemia, hyperthyroidism and low vitamin D levels, have been linked to both osteopenia and sarcopenia. Osteosarcopenia is also commonly observed in older age groups, notably in postmenopausal women. Glucagon-like peptide-1 (GLP-1), a labile incretin secreted from the intestinal L-cells, stimulates insulin secretion and sensitivity, making it an effective anti-diabetic medication.
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