The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer’s disease
Open accessAbstract
Deposition of insoluble protein aggregates is a hallmark of neurodegenerative diseases. The universal presence of β-amyloid and tau in Alzheimer’s disease (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that have dominated AD pathogenesis research and therapeutic development. However, the underlying etiology of the disease remains to be fully elucidated. Here we report a comprehensive study of the human brain-insoluble proteome in AD by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate in the disease, including U1-70K and other U1 small nuclear ribonucleoprotein (U1 snRNP) spliceosome components. Similar accumulations in mild cognitive impairment cases indicate that spliceosome changes occur in early stages of AD. Multiple U1 snRNP subunits form cytoplasmic tangle-like structures in AD but not in other examined neurodegenerative disorders, including Parkinson disease and frontotemporal lobar degeneration. Comparison of RNA from AD and control brains reveals dysregulated RNA processing with accumulation of unspliced RNA species in AD, including myc box-dependent-interacting protein 1, clusterin, and presenilin-1 . U1-70K knockdown or antisense oligonucleotide inhibition of U1 snRNP increases the protein level of amyloid precursor protein. Thus, our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis.
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In the citing paper
“Tau-RBP interactions disrupt RNA splicing resulting in gene dysregulation and neurotoxicity (Apicco et al., 2018; Bai et al., 2013; Hsieh et al., 2019).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Bai et al., 2013
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“We performed a comprehensive analysis of the aggregated proteome, detecting the deposition of U1 small nuclear ribonucleoprotein (U1 snRNP) and a deficit of RNA splicing in AD brain (Bai et al., 2013; Lutz and Peng, 2018).”
From Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression (2020) · cites this paper as Bai et al., 2013
In the citing paper
“We and others have previously identified RNA splicing deficits in AD brain which could have profound impact on transcription of many genes, including tau, APP, and presenilins (Bai et al., 2013; Tollervey et al., 2011).”
From A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer’s Disease (2017) · cites this paper as Bai et al., 2013
In the citing paper
“These ribonucleoproteins, constituents of the spliceosome complex responsible for RNA processing, are mislocalized in AD to the cytoplasm of neuronal cell bodies where they aggregate with NFTs and contribute to widespread alterations in RNA processing [134].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [134]
In the citing paper
“this aggregation of U1 snRNPs with tau appears to be unique to the AD brain and absent among other primary tauopathies, such as FTLD [134, 138].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [134]
In the citing paper
“previous analyses of the AD brain detergent-insoluble proteome, which have repeatedly demonstrated the association of U1 small nuclear ribonucleoproteins (U1 snRNPs) and other RNA-binding proteins with tau tangles [133–137].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [134]
In the citing paper
“Interestingly, our previous studies demonstrated that many of the U1 snRNPs colocalize with neurofibrillary tangles and paired helical filaments in AD brain [24, 32–34], and that accumulation of insoluble snRNPs correlates strongly with both amyloid and Tau pathology [32–37].”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [24]
In the citing paper
“We have previously shown that U1 snRNPs are a major component of the AD insoluble proteome [24, 32–34].”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [24]
In the citing paper
“Although we have previously observed that snRNP alterations are associated with deficits in RNA splicing in AD brain [24, 32]—a finding recently confirmed by others [52]”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [24]
In the citing paper
“This may be due to the fact that U1 spliceosome proteins undergo a dramatic shift in solubility in AD brain, and aggregate in close proximity to neurofibrillary tangles [24, 32–34].”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [24]
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Metadata
- Authors
- Bai, B., Hales, C. M., Chen, P.-C., Gozal, Y., Dammer, E. B., Fritz, J. J., Wang, X., Xia, Q., Duong, D. M., Street, C., Cantero, G., Cheng, D., Jones, D. R., Wu, Z., Li, Y., Diner, I., Heilman, C. J., Rees, H. D., Wu, H., Lin, L., Szulwach, K. E., Gearing, M., Mufson, E. J., Bennett, D. A., Montine, T. J., Seyfried, N. T., Wingo, T. S., Sun, Y. E., Jin, P., Hanfelt, J., Willcock, D. M., Levey, A., Lah, J. J., & Peng, J.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Emory University (US)
- Departments of Structural Biology and Developmental Neurobiology and
- Human Genetics,
- University of California, Los Angeles (US)
- Biostatistics and Bioinformatics,
- Rush University Medical Center (US)
- University of Washington (US)
- University of Kentucky (US)
- ORCID
- Bai, Bing
- Hales, Chadwick M.
- Chen, Ping-Chung
- Dammer, Eric B.
- Wang, Xusheng
- Xia, Qiangwei
- Duong, Duc M.
- Cantero, Gloria
- Cheng, Dongmei
- Jones, Drew R.
- Wu, Zhiping
- Li, Yuxin
- Wu, Hao
- Gearing, Marla
- Mufson, Elliott J.
- Bennett, David A.
- Montine, Thomas J.
- Seyfried, Nicholas T.
- Wingo, Thomas S.
- Sun, Yi E.
- Jin, Peng
- Hanfelt, John
- Levey, Allan
- Lah, James J.
- Peng, Junmin
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-09-10
- Volume
- 110
- Issue
- 41
- Pages
- 16562-16567
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3799305
- OpenAlex
- W2075426349
- Semantic Scholar
- b4638372c5d5e262f0ad2963dd66aed83aac9d24
- Cited by
- 335
- References
- 58
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 23 · 2023: 29 · 2022: 23 · 2021: 43 · 2020: 29 · 2019: 24 · 2018: 27 · 2017: 24 · 2016: 30 · 2015: 12 · 2014: 17
- FWCI
- 13.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Lebanese Syrian Associated Charities
- National Institutes of Health
- Instituto de Salud Carlos III
- National Institute on Aging (P01AG014449, F32AG038259, R01AG015819, P30AG010161, R01AG043375, P50AG005136, P50AG025688)
- National Institute of Mental Health (R01MH082068)
- National Cancer Institute (P30CA021765)
- National Institute of General Medical Sciences (P01GM081621, T32GM008169)
- National Institute of Neurological Disorders and Stroke (T32NS007480, F32NS007480, P30NS055077, F30NS057902)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, U1 snRNP, U1-70K, RNA splicing, spliceosome, protein aggregates, amyloid precursor protein, unspliced RNA, mild cognitive impairment, antisense oligonucleotides, clusterin, presenilin 1, neurodegeneration
- MeSH terms
- Alzheimer Disease, Brain, Chromatography, Liquid, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Blotting, Western, Spliceosomes, Alternative Splicing, Ribonucleoprotein, U1 Small Nuclear, Reverse Transcriptase Polymerase Chain Reaction, Proteome, Proteomics, Tandem Mass Spectrometry, High-Throughput Nucleotide Sequencing
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