DCPS modulates TDP-43-linked neurodegeneration
Loss of RNA-binding protein, TDP-43 function, contributes to neurodegeneration.
Using CRISPRi screening in human neurons, the researchers identify decapping scavenger enzyme (DCPS) as a modifier of TDP-43 loss-of-function-mediated toxicity.
TDP-43 interacts with processing bodies (P-bodies) component proteins, potentially influencing their dynamic equilibrium and assembly into ribonucleoprotein (RNP) granules. Loss of TDP-43 hyperactivates P-bodies, increasing mRNA association and RNA decay.
The authors show that reducing DCPS restores RNA turnover, rescues transcriptomic dysregulation via P-body regulation, and improves neuronal survival, revealing a potential therapeutic target for ALS/FTD.
