Although covalent nucleotide modifications were first identified on the bases of transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), a number of these epitranscriptome marks have also been found to occur on the bases of messenger RNAs (mRNAs). These covalent mRNA features have been demonstrated to have various and significant effects on the processing (e.g. splicing, polyadenylation, etc.) and functionality (e.g. translation, transport, etc.) of these protein-encoding molecules. Here, we focus our attention on the current understanding of the collection of covalent nucleotide modifications known to occur on mRNAs in plants, how they are detected and studied, and the most outstanding future questions of each of these important epitranscriptomic regulatory signals.
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http://dx.doi.org/10.1093/plcell/koad044 | DOI Listing |
Epilepsia
January 2025
Atalanta Therapeutics, Boston, Massachusetts, USA.
Objective: Gain-of-function variants in the KCNT1 gene, which encodes a sodium-activated potassium ion channel, drive severe early onset developmental epileptic encephalopathies including epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. No therapy provides more than sporadic or incremental improvement. Here, we report suppression of seizures in a genetic mouse model of KCNT1 epilepsy by reducing Kcnt1 transcript with divalent small interfering RNA (siRNA), an emerging variant of oligonucleotide technology developed for the central nervous system.
View Article and Find Full Text PDFNat Commun
January 2025
University of St Andrews, School of Biology, North Haugh, Biomolecular Sciences Building, St Andrews, UK.
Cyclic dipeptides are produced by organisms across all domains of life, with many exhibiting anticancer and antimicrobial properties. Oxidations are often key to their biological activities, particularly C-C bond oxidation catalysed by tailoring enzymes including cyclodipeptide oxidases. These flavin-dependent enzymes are underexplored due to their intricate three-dimensional arrangement involving multiple copies of two distinct small subunits, and mechanistic details underlying substrate selection and catalysis are lacking.
View Article and Find Full Text PDFBiochimie
January 2025
Laboratory of Antimicrobial Resistance, Institute of Ecological and Agricultural Biology (X-BIO), Tyumen State University, Tyumen, Russia.
Macrolactin A (McA) is a secondary metabolite produced by Bacillus species. It has been known for its antimicrobial properties since the late 1980s, although the exact mechanism of its antibacterial activity remains unknown. In this study, we have found that McA is an inhibitor of protein synthesis in bacteria.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
DNPH1 is responsible for eliminating the epigenetically modified nucleotide, 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate (hmdUMP), preventing formation of hmdUTP, a mutation-inducing nucleotide. Loss of DNPH1 activity sensitizes PARP inhibition-resistant BRCA-deficient cancers by causing incorporation of hmdUTP into DNA. Hydrolysis of hmdUMP by DNPH1 proceeds through a covalent intermediate between Glu104 and 2-deoxyribose 5-phosphate, followed by hydrolysis, a reaction cycle with two transition states.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Non-covalent interactions of poly(ADP-ribose) (PAR) facilitate condensate formation, yet the impact of these interactions on condensate properties remains unclear. Here, we demonstrate that PAR-mediated interactions through PARP13, specifically the PARP13.2 isoform, are essential for modulating the dynamics of stress granules-a class of cytoplasmic condensates that form upon stress, including types frequently observed in cancers.
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