ALS Compendium

Title: Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43

Year Published: 2011

Observation: TDP43 binds GU rich distal intronic sites. RNAs altered after in vivo TDP43 depletion in mouse brain. TDP43 binding to long pre mRNAs sustains their levels. TDP43 mediates alternative splicing of its mRNA targets. TDP43 autoregulates through binding on its 3' UTR

Comment: TDP-43 autoregulates its synthesis, in part by directly binding and enhancing splicing of an intron in the 3' untranslated region of its own transcript, thereby triggering nonsense-mediated RNA degradation.

Citation: Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Huelga, S. C., Moran, J., Liang, T. Y., … Cleveland, D. W. (2011). Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nature Neuroscience, 14(4), 459–68. doi:10.1038/nn.2779

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