DOI: 10.1073/pnas.1315438110. RAN proteins and RNA foci from antisense transcripts in <i>C9ORF72</i> ALS and frontotemporal dementia

RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia

10.1073/pnas.1315438110

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Significance A GGGGCC expansion mutation located in intron 1 of chromosome 9 ORF 72 ( C9ORF72 ) was recently described as a common cause of familial amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). We show that this single mutation results in the accumulation of sense and antisense RNA foci plus six expansion proteins expressed by repeat-associated non-ATG (RAN) translation. RNAs accumulate in nuclear foci and the RAN proteins form cytoplasmic aggregates in neurons that often cluster in affected brain regions. These results indicate that bidirectional transcription and RAN translation are fundamental pathologic features of C9ORF72 ALS/FTD. Additionally these data have broad implications that change our understanding of how microsatellite expansion mutations are expressed in patient cells and how they cause disease.

Bibliography

Zu, T., Liu, Y., BaÃ±ez-Coronel, M., Reid, T., Pletnikova, O., Lewis, J., Miller, T. M., Harms, M. B., Falchook, A. E., Subramony, S. H., Ostrow, L. W., Rothstein, J. D., Troncoso, J. C., & Ranum, L. P. W. (2013). RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proceedings of the National Academy of Sciences, 110(51).

Authors 14

Tao Zu (first)
Yuanjing Liu (additional)
Monica Bañez-Coronel (additional)
Tammy Reid (additional)
Olga Pletnikova (additional)
Jada Lewis (additional)
Timothy M. Miller (additional)
Matthew B. Harms (additional)
Annet E. Falchook (additional)
S. H. Subramony (additional)
Lyle W. Ostrow (additional)
Jeffrey D. Rothstein (additional)
Juan C. Troncoso (additional)
Laura P. W. Ranum (additional)

References 31 Referenced 696

Dates

Type	When
Created	11 years, 9 months ago (Nov. 18, 2013, 11:49 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 10:49 p.m.)
Indexed	1 hour, 4 minutes ago (Aug. 29, 2025, 7:52 a.m.)
Issued	11 years, 9 months ago (Nov. 18, 2013)
Published	11 years, 9 months ago (Nov. 18, 2013)
Published Online	11 years, 9 months ago (Nov. 18, 2013)
Published Print	11 years, 8 months ago (Dec. 17, 2013)

Funders 0

None

BibTeX

@article{Zu_2013, title={RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia}, volume={110}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1315438110}, DOI={10.1073/pnas.1315438110}, number={51}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Zu, Tao and Liu, Yuanjing and Bañez-Coronel, Monica and Reid, Tammy and Pletnikova, Olga and Lewis, Jada and Miller, Timothy M. and Harms, Matthew B. and Falchook, Annet E. and Subramony, S. H. and Ostrow, Lyle W. and Rothstein, Jeffrey D. and Troncoso, Juan C. and Ranum, Laura P. W.}, year={2013}, month=nov }

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