Paraspeckle condensation is controlled via TDP-43 polymerization and linked to neuroprotection - PubMed
5 hours ago
- #Paraspeckle
- #TDP-43
- #Neuroprotection
- Paraspeckle condensation is regulated by TDP-43 polymerization and associated with neuroprotection.
- TDP-43 inhibits NEAT1_2 ribonucleoprotein particle condensation into paraspeckles in a concentration-dependent manner, requiring intact polymerization and RNA binding.
- Core paraspeckle proteins like FUS counterbalance TDP-43's inhibitory effect.
- Under stress, TDP-43 sequestration into nuclear condensates reduces paraspeckle suppression and enhances their dynamism.
- NEAT1_2 middle-part and 3'-end UG repeats mediate paraspeckle regulation by TDP-43 both cotranscriptionally and post-assembly.
- Deletion of the 3'-end UG repeat increases paraspeckle stability and cytoprotection in stressed human neurons.
- Longer 3'-end UG repeats correlate with shorter survival in amyotrophic lateral sclerosis (ALS).