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http://dx.doi.org/10.1038/229258a0 | DOI Listing |
J Med Chem
January 2025
Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai 201203, China.
Protein arginine methyltransferase 5 (PRMT5), which catalyzes the symmetric dimethylation of arginine residues on target proteins, plays a critical role in gene expression regulation, RNA processing, and signal transduction. Aberrant PRMT5 activity has been implicated in cancers and other diseases, making it a potential therapeutic target. Here, we report the discovery of a methylthioadenosine (MTA) cooperative PRMT5 inhibitor.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Biology, Center for RNA Biology, University of Rochester, Rochester, NY, USA. Electronic address:
The tRNA methyltransferase 1 (TRMT1) enzyme catalyzes the N2,N2-dimethylguanosine (m2,2G) modification in tRNAs. Intriguingly, vertebrates encode an additional tRNA methyltransferase 1-like (TRMT1L) paralog. Here, we use a comprehensive tRNA sequencing approach to decipher targets of human TRMT1 and TRMT1L.
View Article and Find Full Text PDFBiol Open
December 2024
Department of Dermatology, University of Zurich, University Hospital Zurich, Schlieren CH-8952, Switzerland.
The gonadal anchor cell (AC) is an essential organizer for the development of the egg-laying organ in the C. elegans hermaphrodite. Recent work has investigated the mechanisms that control the quiescent state the AC adopts while fulfilling its functions.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background: The nuclear clearance and cytoplasmic aggregation of splicing repressor TAR DNA/RNA-binding protein-43 (TDP-43) occur in approximately 50% of Alzheimer's disease (AD) cases and about 45% of frontotemporal dementia (FTD). However, it is not clear how early such mechanism occurs in AD and FTD as there is no method of detecting TDP-43 dysregulation in living individuals. Since the loss of nuclear TDP-43 leads to cryptic exon inclusion, we propose that cryptic exon-encoded peptides may be detected in patient biofluids as biomarkers of TDP-43 loss of function.
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