Small RNA modifications in Alzheimer's disease
BackgroundWhile significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associ...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996120303338 |
| _version_ | 1818337265033674752 |
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| author | Xudong Zhang Fatima Trebak Lucas A.C. Souza Junchao Shi Tong Zhou Patrick G. Kehoe Qi Chen Yumei Feng Earley |
| author_facet | Xudong Zhang Fatima Trebak Lucas A.C. Souza Junchao Shi Tong Zhou Patrick G. Kehoe Qi Chen Yumei Feng Earley |
| author_sort | Xudong Zhang |
| collection | DOAJ |
| description | BackgroundWhile significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications are important regulators of complex physiological and pathological processes, including aging, stress responses, and epigenetic inheritance. However, whether small RNAs and their modifications are altered in dementia is not known.MethodsWe performed LC-MS/MS–based, high-throughput assays of small RNA modifications in post-mortem samples of the prefrontal lobe cortices of Alzheimer's disease (AD) and control individuals. We noted that some of the AD patients has co-occurring vascular cognitive impairment-related pathology (VaD).FindingsWe report altered small RNA modifications in AD samples compared with normal controls. The 15–25-nucleotide (nt) RNA fraction of these samples was enriched for microRNAs, whereas the 30–40-nt RNA fraction was enriched for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). Interestingly, most of these altered RNA modifications were detected both in the AD and AD with co-occurring vascular dementia subjects. In addition, sequencing of small RNA in the 30–40-nt fraction from AD cortices revealed reductions in rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg.InterpretationThese data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer's disease.FundNIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe. |
| first_indexed | 2024-12-13T14:52:28Z |
| format | Article |
| id | doaj.art-523000f0e25d49efa6ff31ca916d1380 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T14:52:28Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-523000f0e25d49efa6ff31ca916d13802022-12-21T23:41:18ZengElsevierNeurobiology of Disease1095-953X2020-11-01145105058Small RNA modifications in Alzheimer's diseaseXudong Zhang0Fatima Trebak1Lucas A.C. Souza2Junchao Shi3Tong Zhou4Patrick G. Kehoe5Qi Chen6Yumei Feng Earley7Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USADepartments of Pharmacology, Physiology & Cell Biology, Center for Molecular & Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, School of Medicine, Reno, NV, USADepartments of Pharmacology, Physiology & Cell Biology, Center for Molecular & Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, School of Medicine, Reno, NV, USADivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USADepartments of Physiology & Cell Biology, University of Nevada, Reno, School of Medicine, Reno, NV, USADementia Research Group, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USA; Correspondence to: Y. Feng Earley, Pharmacology and Physiology & Cell Biology, Center for Molecular & Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, School of Medicine, 1664 North Virginia Street, Mail-stop 0318, Reno, NV 89557, USA.Departments of Pharmacology, Physiology & Cell Biology, Center for Molecular & Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, School of Medicine, Reno, NV, USA; Correspondence to: Q. Chen, Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA.BackgroundWhile significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications are important regulators of complex physiological and pathological processes, including aging, stress responses, and epigenetic inheritance. However, whether small RNAs and their modifications are altered in dementia is not known.MethodsWe performed LC-MS/MS–based, high-throughput assays of small RNA modifications in post-mortem samples of the prefrontal lobe cortices of Alzheimer's disease (AD) and control individuals. We noted that some of the AD patients has co-occurring vascular cognitive impairment-related pathology (VaD).FindingsWe report altered small RNA modifications in AD samples compared with normal controls. The 15–25-nucleotide (nt) RNA fraction of these samples was enriched for microRNAs, whereas the 30–40-nt RNA fraction was enriched for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). Interestingly, most of these altered RNA modifications were detected both in the AD and AD with co-occurring vascular dementia subjects. In addition, sequencing of small RNA in the 30–40-nt fraction from AD cortices revealed reductions in rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg.InterpretationThese data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer's disease.FundNIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe.http://www.sciencedirect.com/science/article/pii/S0969996120303338Non-coding RNAAlzheimer's diseasePrefrontal cortexEpigenetics |
| spellingShingle | Xudong Zhang Fatima Trebak Lucas A.C. Souza Junchao Shi Tong Zhou Patrick G. Kehoe Qi Chen Yumei Feng Earley Small RNA modifications in Alzheimer's disease Neurobiology of Disease Non-coding RNA Alzheimer's disease Prefrontal cortex Epigenetics |
| title | Small RNA modifications in Alzheimer's disease |
| title_full | Small RNA modifications in Alzheimer's disease |
| title_fullStr | Small RNA modifications in Alzheimer's disease |
| title_full_unstemmed | Small RNA modifications in Alzheimer's disease |
| title_short | Small RNA modifications in Alzheimer's disease |
| title_sort | small rna modifications in alzheimer s disease |
| topic | Non-coding RNA Alzheimer's disease Prefrontal cortex Epigenetics |
| url | http://www.sciencedirect.com/science/article/pii/S0969996120303338 |
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