↓ Skip to main content

Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy

Overview of attention for article published in Acta Neuropathologica, May 2015
Altmetric Badge

About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (91st percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

Mentioned by

news
2 news outlets
twitter
6 tweeters

Citations

dimensions_citation
72 Dimensions

Readers on

mendeley
146 Mendeley
Title
Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy
Published in
Acta Neuropathologica, May 2015
DOI 10.1007/s00401-015-1429-9
Pubmed ID
Authors

Johnathan Cooper-Knock, Adrian Higginbottom, Matthew J. Stopford, J. Robin Highley, Paul G. Ince, Stephen B. Wharton, Stuart Pickering-Brown, Janine Kirby, Guillaume M. Hautbergue, Pamela J. Shaw

Abstract

GGGGCC repeat expansions of C9ORF72 represent the most common genetic variant of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We and others have proposed that RNA transcribed from the repeat sequence is toxic via sequestration of RNA-binding factors. Both GGGGCC-repeat (sense) and CCCCGG-repeat (antisense) molecules are detectable by fluorescence in situ hybridisation as RNA foci, but their relative expression pattern within the CNS and contribution to disease has not been determined. Blinded examination of CNS biosamples from ALS patients with a repeat expansion of C9ORF72 showed that antisense foci are present at a significantly higher frequency in cerebellar Purkinje neurons and motor neurons, whereas sense foci are present at a significantly higher frequency in cerebellar granule neurons. Consistent with this, inclusions containing sense or antisense derived dipeptide repeat proteins were present at significantly higher frequency in cerebellar granule neurons or motor neurons, respectively. Immunohistochemistry and UV-crosslinking studies showed that sense and antisense RNA molecules share similar interactions with SRSF2, hnRNP K, hnRNP A1, ALYREF, and hnRNP H/F. Together these data suggest that, although sense and antisense RNA molecules might be expected to be equally toxic via their shared protein binding partners, distinct patterns of expression in various CNS neuronal populations could lead to relative differences in their contribution to the pathogenesis of neuronal injury. Moreover in motor neurons, which are the primary target of pathology in ALS, the presence of antisense foci (χ (2), p < 0.00001) but not sense foci (χ (2), p = 0.75) correlated with mislocalisation of TDP-43, which is the hallmark of ALS neurodegeneration. This has implications for translational approaches to C9ORF72 disease, and furthermore interacting RNA-processing factors and transcriptional activators responsible for antisense versus sense transcription might represent novel therapeutic targets.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 146 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 <1%
United Kingdom 1 <1%
Unknown 144 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 41 28%
Student > Bachelor 23 16%
Researcher 23 16%
Student > Master 18 12%
Unspecified 14 10%
Other 27 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 43 29%
Neuroscience 31 21%
Biochemistry, Genetics and Molecular Biology 28 19%
Unspecified 18 12%
Medicine and Dentistry 14 10%
Other 12 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 19. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 August 2018.
All research outputs
#833,524
of 13,337,884 outputs
Outputs from Acta Neuropathologica
#138
of 1,660 outputs
Outputs of similar age
#18,936
of 231,059 outputs
Outputs of similar age from Acta Neuropathologica
#5
of 32 outputs
Altmetric has tracked 13,337,884 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,660 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.1. This one has done particularly well, scoring higher than 91% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 231,059 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.