ALS

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD

Summary This study demonstrates that loss of TDP-43 function leads to widespread cryptic splicing events that produce novel protein isoforms not normally expressed in healthy cells. These de novo proteins may contribute to the pathogenesis of ALS and FTD by triggering immune responses or impairing cellular functions.

Amyotrophic Lateral Sclerosis associated FUS mutation shortens mitochondria and induces neurotoxicity

Summary This study shows that disease-associated FUS mutations cause mitochondrial shortening and fragmentation in neurons, leading to neurotoxicity. The findings connect FUS dysfunction to mitochondrial dynamics, providing a potential mechanism for neurodegeneration in ALS patients carrying FUS mutations.

FUS regulates genes coding for RNA-binding proteins in neurons by binding to their highly conserved introns

Summary CLIP-seq analysis reveals that FUS, an ALS-associated RNA-binding protein, preferentially binds to highly conserved intronic sequences of genes encoding other RNA-binding proteins in neurons. This autoregulatory network suggests a mechanism by which FUS dysfunction could broadly disrupt neuronal RNA metabolism.

Identification of in vivo, conserved, TAF15 RNA binding sites reveals the impact of TAF15 on the neuronal transcriptome

Summary Using CLIP-seq, this study identifies the in vivo binding sites of TAF15, an ALS-associated RNA-binding protein, across the neuronal transcriptome. The findings reveal evolutionarily conserved binding sites and provide insight into the role of TAF15 in neuronal RNA metabolism.