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Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of FSHD
Open accessPreprint — published as 10.7554/elife.41740
Abstract
DUX4 is a transcription factor whose misexpression in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). While DUX4’s transcriptional activity has been extensively characterized, the DUX4-induced proteome remains undescribed. Here, we report concurrent measurement of RNA and protein levels in DUX4-expressing cells via RNA-seq and quantitative mass spectrometry. DUX4 transcriptional targets were robustly translated, confirming the likely clinical relevance of proposed FSHD biomarkers. However, a multitude of mRNAs and proteins exhibited discordant expression changes upon DUX4 expression. Our dataset revealed unexpected proteomic, but not transcriptomic, dysregulation of diverse molecular pathways, including Golgi apparatus fragmentation, as well as extensive post-transcriptional buffering of stress response genes. Key components of RNA degradation machineries, including UPF1, UPF3B, and XRN1, exhibited suppressed protein, but not mRNA, levels, explaining the build-up of aberrant RNAs that characterizes DUX4-expressing cells. Our results provide a resource for the FSHD community and illustrate the importance of post-transcriptional processes to DUX4-induced pathology.
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Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566
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Research works printed but not linked: 30
- 10.1186/2044-5040-4-12 · DOI
- 10.1126/science.1189044 · DOI
- 10.1016/j.devcel.2011.11.013 · DOI
- 10.1093/hmg/ddt314 · DOI
- 10.1371/journal.pgen.1003947 · DOI
- 10.1098/rsif.2014.0797 · DOI
- Feng Q , et al. (2015) A feedback loop between nonsense-mediated decay and the retrogene DUX4 in facioscapulohumeral muscular dystrophy. Elife 4. · DOI
- 10.1002/acn3.158 · DOI
- 2016, DUX4-induced constitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients, Free Radic Biol Med, 99, 244, 10.1016/j.freeradbiomed.2016.08.007 · DOI
- 10.1371/journal.pgen.1006658 · DOI
- Campbell AE , Belleville A , Resnick R , Shadle SC , & Tapscott SJ (2018) Facioscapulohumeral dystrophy: Activating an early embryonic transcriptional program in human skeletal muscle. Hum Mol Genet. · DOI
- 10.1016/j.molmed.2015.02.011 · DOI
- 10.1111/j.1582-4934.2012.01647.x · DOI
- 10.1093/hmg/ddv315 · DOI
- 10.1242/jcs.180372 · DOI
- 10.1371/journal.pone.0051865 · DOI
- 10.1002/pmic.200600056 · DOI
- 10.1007/s00109-004-0583-7 · DOI
- 2016, Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells, Hum Mol Genet, 25, 4419
- 10.1038/nprot.2008.2 · DOI
- 10.1093/hmg/ddu251 · DOI
- 10.1016/j.bbamcr.2005.04.007 · DOI
- 10.3390/ijms140918670 · DOI
- 10.1038/emboj.2013.80 · DOI
- 10.1016/B978-0-12-385114-7.00004-0 · DOI
- 10.1093/bfgp/els051 · DOI
- 10.1021/ac025529o · DOI
- 10.1038/nmeth1113 · DOI · Paper page
- 10.1016/j.jprot.2012.04.035 · DOI
- 10.1038/nprot.2006.427 · DOI
Metadata
- Authors
- Jagannathan, S., Ogata, Y., Gafken, P. R., Tapscott, S. J., & Bradley, R. K.
- Affiliations
- Fred Hutch Cancer Center (US)
- Corresponding author
- Jagannathan, Sujatha
- Tapscott, Stephen J.
- Bradley, Robert K.
- Venue
- eLife
- Publisher
- openRxiv
- Published
- 2018-09-14
- Volume
- 8
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6349399
- OpenAlex
- W2892060349
- Cited by
- 63
- References
- 1
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 26 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 2
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- M.J. Murdock Charitable Trust
- Leukemia and Lymphoma Society
- FSH Society (FSHS-22014-01)
- National Institutes of Health (1s10od020069-01, CA015704, NINDS P01NS069539)
- National Cancer Institute (P30CA015704)
- National Institute of Neurological Disorders and Stroke (P01NS069539)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR045203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- facioscapulohumeral muscular dystrophy, DUX4, post-transcriptional regulation, Golgi fragmentation, stress response genes, UPF1, UPF3B, Xrn1, skeletal muscle
- MeSH terms
- Cell Line, Gene Expression Regulation, Humans, RNA, Stress, Physiological, Transcription, Genetic, Homeodomain Proteins, Muscular Dystrophy, Facioscapulohumeral, Proteomics
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