Abstract
Diced Triplets Expose Neurons to RISC
Highlights
Cytotoxic effects are triggered by expanded CAG repeats, but not by expanded CAA repeats, consistent with recent findings in a fly model [11]. sCAG species were detected in Ago-2 complexes, supporting association with RNAi pathways
Antisense inhibitors of the sCAG species reverse cytotoxicity, and sCAGs were detected in R6/2 Huntington’s disease (HD) transgenic mice and in postmortem human HD brain tissue. sCAGs isolated from human HD tissue and transfected into cells induced toxicity
It is noteworthy that a DM1 antisense transcript containing the repeat in the CAG orientation is converted to 21-nt fragments that include CAG units [20], similar to the 21-nt sCAG fragments from the HD locus reported by Banez-Coronel et al [19]
Summary
[15,16]. A second potential mechanism of CAG/CTG toxicity emerged from evidence that bidirectional transcription through the HTT repeat region [17] is a source of Dicer-generated CAG/CUG repeat siRNAs capable of targeting cellular transcripts containing complementary repeats [18]. A second potential mechanism of CAG/CTG toxicity emerged from evidence that bidirectional transcription through the HTT repeat region [17] is a source of Dicer-generated CAG/CUG repeat siRNAs capable of targeting cellular transcripts containing complementary repeats [18]. In this issue of PLoS Genetics, BanezCoronel and colleagues [19] provide further evidence for the involvement of HTT RNA and the RNAi pathway in HD pathogenesis.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
