Title | tRNA-Derived Fragments in Alzheimer's Disease: Implications for New Disease Biomarkers and Neuropathological Mechanisms. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Wu, W, Lee, I, Spratt, H, Fang, X, Bao, X |
Journal | J Alzheimers Dis |
Volume | 79 |
Issue | 2 |
Pagination | 793-806 |
Date Published | 2021 |
ISSN | 1875-8908 |
Keywords | Aged, Alzheimer Disease, Biomarkers, Blotting, Northern, Case-Control Studies, Hippocampus, Humans, Polymerase Chain Reaction, RNA, Small Untranslated, RNA, Transfer |
Abstract | BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia caused by irreversible neurodegeneration, with the onset mechanisms elusive. tRNA-derived RNA fragments (tRFs), a recently discovered family of small non-coding RNAs (sncRNAs), have been found to associate with many human diseases, including infectious, metabolic, and neurological diseases. However, whether tRFs play a role in human AD development is not known. OBJECTIVE: This study aimed to explore whether tRFs are involved in human AD. METHODS: Thirty-four postmortem human hippocampus samples were used. The expression of Drosha, Dicer, and angiogenin (ANG), three ribonucleases responsible for the biogenesis of sncRNAs, was determined by qRT-PCR and western blot. The tRFs in the hippocampus was detected by qRT-PCR or northern blot. We also used qRT-PCR to quantify NOP2/Sun RNA methyltransferase 2 (NSun2) and polyadenylation factor I subunit 1 (CLP1), two tRNA modification enzymes. RESULTS: tRFs derived from a subset of tRNAs are significantly altered in the hippocampus of AD patients. The expression change of some tRFs showed age- and disease stage-dependent. ANG is significantly enhanced in AD, suggesting its role in inducing tRFs in AD. The expression of NSun2 in AD patients younger than 65 was significantly decreased. According to a previous report supporting NSun2-mediated tRNA methylation modification making tRNA less susceptible to ANG-mediated cleavage, our results suggested that the decrease in NSun2 may make tRNAs less methylated and subsequently enhanced tRF production from ANG-mediated tRNA cleavage. CONCLUSION: Our studies demonstrated for the first time the involvement of tRFs in human AD. |
DOI | 10.3233/JAD-200917 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 33337366 |
PubMed Central ID | PMC8485948 |
Grant List | R01 AI116812 / AI / NIAID NIH HHS / United States R21 AG069226 / AG / NIA NIH HHS / United States |