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Small RNA modifications in Alzheimer's disease

Zhang, Xudong ; Trebak, Fatima ; Souza, Lucas A.C. ; Shi, Junchao ; Zhou, Tong ; Kehoe, Patrick G. ; Chen, Qi ; Feng Earley, Yumei

Neurobiology of disease, 2020-11, Vol.145, p.105058-105058, Article 105058 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    Small RNA modifications in Alzheimer's disease
  • Autor: Zhang, Xudong ; Trebak, Fatima ; Souza, Lucas A.C. ; Shi, Junchao ; Zhou, Tong ; Kehoe, Patrick G. ; Chen, Qi ; Feng Earley, Yumei
  • Assuntos: Alzheimer's disease ; Epigenetics ; Non-coding RNA ; Prefrontal cortex
  • É parte de: Neurobiology of disease, 2020-11, Vol.145, p.105058-105058, Article 105058
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Credit Author Statement
    Xudong Zhang: Methodology, Data curation, Writing-part of the original draft preparation, Fatima Trebak: Methodology Data curation, Lucas AC Souza: Writing, Review, Editing, Data analysis, Junchao Shi: Software, Data analysis, Tong Zhou: Software, statistical analysis, Editting; Patrick G. Kehoe; Curation of patients information, Writing-Reviewing and Editing, Qi Chen: Conceptualization, Methodology, Writing-Reviewing and Editing, Yumei Feng Earley: Conceptualization, Methodology, Writing-Reviewing and Editing.
    Contributed equally to this work
  • Descrição: Background While 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. Methods We 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). Findings We 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. Interpretation These data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer's disease. Fund NIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe. [Display omitted] •Alzheimer's disease (AD) and vascular dementia (VaD) are marked by cognitive impairment and neuropathologies caused by significant neuronal death.•Epigenetic changes are risk factors for the development of dementia.•High-throughput liquid chromatography-tandem mass spectrometry profiles small RNA modifications.•Small RNA modifications in the prefrontal cortex are altered in Alzheimer's disease.•tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs) are altered in Alzheimer's disease.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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