ALS-linked RNA-binding proteins regulate dominant-negative isoform of TDP-43

Neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration are linked to dysregulated TDP-43, an RNA-binding protein (RBP) encoded by the TARDBP gene. 

In this study, the researchers identified a dominant-negative isoform of TDP-4 among the multiple TARDBP splicing variants.

They also demonstrate that ALS-associated RBPs regulate its expression. For example, hnRNP K promotes its splicing and expression, while hnRNP A1 and FUS suppress these processes through distinct mechanisms.

The authors suggest disruptions in RBP network may contribute to ALS pathogenesis.

https://rupress.org/jcb/article/224/10/e202406097/278187/Dominant-negative-isoform-of-TDP-43-is-regulated

https://sciencemission.com/Dominant-negative-isoform-of-TDP-43