Different Stability and Proteasome-Mediated Degradation Rate of SMN Protein Isoforms.

摘要: The key pathogenic steps leading to spinal muscular atrophy (SMA), a genetic disease characterized by selective motor neuron degeneration, are not fully clarified. full-length SMN protein (FL-SMN), the main product of gene SMN1, plays an established role in cytoplasm snRNP biogenesis ultimately mRNA splicing within nucleus. It is also involved axonal transport. However, what extent impairment these two functions contributes SMA pathogenesis remains unknown. A shorter isoform, axonal-SMN or a-SMN, with more specific localization, has been discovered, but whether it might act concert FL-SMN known. As first step defining common divergent intracellular roles vs a-SMN proteins, we here turn-over both proteins and investigated which pathway contributed degradation. We performed real time western blot confocal immunofluorescence analysis easily controllable vitro settings. analyzed co-transfected NSC34 HeLa cells cell clones stably expressing after blocking transcript synthesis inhibition known degradation pathways. Our data indicated that whereas stability transcripts was comparable, much half-life than FL-SMN. In addition, as already demonstrated for FL-SMN, Ub/proteasome played major hypothesize faster rate related protection provided complex assembled. diverse C-terminus may dictate different interactions formation explaining localization neuronal compartment, lower expression a-SMN.