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Co-regulated Transcription Termination by SMN, FUS, TDP-43, and arginine dimethylation of the RNA Polymerase II CTD

GSE134332 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2026/03/06 Platform GPL16791
Summary
The carboxy-terminal domain (CTD) of the RNA polymerase II (RNAPII) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodelling. We previously found that symmetrical demethylation (me2s) of a CTD Arginine residue (R1810 in human) causes recruitment of the Tudor domain of SMN, which interacts with Senataxin. SMN is mutated in spinal muscular atrophy (SMA), and Senataxin is sometimes mutated in Amyotrophic Lateral Sclerosis (ALS). R1810me2s and SMN, like Senataxin, are important for resolving R-loops (DNA:RNA hybrids) at transcription terminators. FUS and TDP-43 (TARDBP) are DNA/RNA binding proteins that are sometimes mutated in ALS and FTD (Frontotemporal dementia). Here we show that TDP-43 and, to some extent, FUS are recruited by the R1810me2s-SMN pathway. Defects in FUS and TDP-43 recruitment influence RNAPII termination and R-loop accumulation, leading to elevated DNA damage at terminators that may contribute to neurodegenerative disorders like ALS and FTD.
Published in
RNA-binding proteins TDP-43 and FUS promote R-loop resolution and regulate transcription termination
Zhao DY, Nabeel-Shah S, Ni Z et al. · The Journal of biological chemistry 2026 · PMID 41796799 · doi:10.1016/j.jbc.2026.111348
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Also filed as BioProject PRJNA554792 and SRA study SRP214781. Searching any of these in the dataset finder brings you back here.

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