More RNA-binding proteins implicated in ALS

Diverse mechanisms have been identified in the motor neuron loss in amyotrophic lateral sclerosis (ALS) 

The ALS-associated RNA-binding protein (RBP) TDP-43 is known to promote UNC13A expression, whose dysregulation is linked to ALS pathogenesis.

The researchers in this study found contribution of three more RBPs indicating functional convergence of ALS-associated RBPs on the regulation of UNC13A expression.

Loss of the RBPs MATR3, FUS, or hnRNPA1 leads to UNC13A repression independently of TDP-43 dysfunction.

The authors show that MATR3, FUS, and hnRNPA1 suppress the expression of the transcriptional repressor REST by destabilizing its mRNA. They also demonstrate that overexpression of REST due to the loss of the three RBPs results in its binding to the UNC13A promoter and subsequent repression of UNC13A transcription.

The researchers found that REST is upregulated in ALS motor neurons.

https://www.embopress.org/doi/full/10.1038/s44318-025-00506-0

https://sciencemission.com/ALS-associated-RNA-binding-proteins