. Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy. Acta Neuropathol. 2015 Jul;130(1):63-75. Epub 2015 May 6 PubMed.


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  1. Cooper-Knock and colleagues report the presence of increased antisense foci in motor neurons relative to sense foci. There are a few possible reasons why this may occur:

    1) It is possible that there is increased transcription of antisense RNA relative to sense RNA.  It would be interesting to see a comprehensive analysis done on both control and C9 patients in different tissues to measure the relative rates of transcription of both the sense and antisense RNA levels.  There might be cell-type specific transcriptional proteins that regulate the transcription of sense vs. antisense RNA. 

    In my view, understanding how high levels of antisense RNA are generated in C9ORF72 patient cells is an open question and needs to be explored further. 

    2) A second possibility would be that the sense and antisense strands maintain different conformations or stabilities.  It has been reported previously that the sense strand forms G-quadruplexes whereas the antisense strand does not (Reddy et al., 2013).  The stability/conformation of these RNAs might be regulated in a cell-specific manner.  It would be interesting to know what the half-life of each RNA species is and whether this varies by cell type.  


    . The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures. J Biol Chem. 2013 Apr 5;288(14):9860-6. PubMed.

    View all comments by Brian Freibaum

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