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Comment
. 2012;8(2):e1002545.
doi: 10.1371/journal.pgen.1002545. Epub 2012 Feb 23.

Diced triplets expose neurons to RISC

Dobrila D Rudnicki  1 , Russell L Margolis, Christopher E Pearson, Wlodzimierz J Krzyzosiak
Affiliations
Comment

Diced triplets expose neurons to RISC

Dobrila D Rudnicki et al. PLoS Genet. 2012.
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. RNA contribution to HD pathogenesis.
An HTT transcript with an expanded CAG repeat is expressed and translated into the huntingtin protein containing an expanded polyglutamine tract. The expanded polyglutamine tract leads to cell toxicity through multiple pathways. It is possible that RAN (Repeat Associated Non-ATG Translation) could generate polypeptides containing polyglutamine, polyalanine, or polyserine tracts that contribute to pathogenesis. In parallel, the expanded repeat in the transcript forms a hairpin that is cleaved by Dicer into 21-nt fragments that lead to toxicity, at least in part based on silencing of other genes that contain CUG and CAG repeats. In addition, HTT transcripts with expanded CAG repeats may accumulate into RNA foci, sequestering RNA binding proteins like MBNL1, leading to toxicity via mechanisms that most likely include aberrant gene splicing. A transcript antisense to the HTT gene may also participate in disease pathogenesis through dysregulation of the HTT sense transcript, formation of sCUG, and/or formation of RNA foci with protein sequestration.
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