Aspects of degradation and translation of the expanded C9orf72 hexanucleotide repeat RNA.

Autor: Mori K; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan., Gotoh S; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan., Ikeda M; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2023 Jul; Vol. 166 (2), pp. 156-171. Date of Electronic Publication: 2023 Jun 05.
DOI: 10.1111/jnc.15847
Abstrakt: An hexanucleotide repeat expansion mutation in the non-coding region of C9orf72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis. This mutation is estimated to be the most frequent genetic cause of these currently incurable diseases. Since the mutation causes autosomal dominantly inherited diseases, disease cascade essentially starts from the expanded DNA repeats. However, molecular disease mechanism is inevitably complex because possible toxic entity for the disease is not just functional loss of translated C9ORF72 protein, if any, but potentially includes bidirectionally transcribed expanded repeat containing RNA and their unconventional repeat-associated non-AUG translation products in all possible reading frames. Although the field learned so much about the disease since the identification of the mutation in 2011, how the expanded repeat causes a particular type of fronto-temporal lobe dominant neurodegeneration and/or motor neuron degeneration is not yet clear. In this review, we summarize and discuss the current understandings of molecular mechanism of this repeat expansion mutation with focuses on the degradation and translation of the repeat containing RNA transcripts.
(© 2023 International Society for Neurochemistry.)
Databáze: MEDLINE
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