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Differential expression of m5C RNA methyltransferase genes NSUN6 and NSUN7 in Alzheimer’s disease and traumatic brain injury

Perez Grovas-Saltijeral, Adriana; Rajkumar, Anto P.; Knight, Helen Miranda

Differential expression of m5C RNA methyltransferase genes NSUN6 and NSUN7 in Alzheimer’s disease and traumatic brain injury Thumbnail


Adriana Perez Grovas-Saltijeral

Anto P. Rajkumar


Epigenetic processes have become increasingly relevant in understanding disease-modifying mechanisms. 5-Methylcytosine methylations of DNA (5mC) and RNA (m5C) have functional transcriptional and RNA translational consequences and are tightly regulated by writer, reader and eraser effector proteins. To investigate the involvement of 5mC/5hmC and m5C effector proteins contributing to the development of dementia neuropathology, RNA sequencing data of 31 effector proteins across four brain regions was examined in 56 aged non-affected and 51 Alzheimer’s disease (AD) individuals obtained from the Aging, Dementia and Traumatic Brain Injury Study. Gene expression profiles were compared between AD and controls, between neuropathological Braak and CERAD scores and in individuals with a history of traumatic brain injury (TBI). We found an increase in the DNA methylation writers DNMT1, DNMT3A and DNMT3B messenger RNA (mRNA) and a decrease in the reader UHRF1 mRNA in AD samples across three brain regions whilst the DNA erasers GADD45B and AICDA showed changes in mRNA abundance within neuropathological load groupings. RNA methylation writers NSUN6 and NSUN7 showed significant expression differences with AD and, along with the reader ALYREF, differences in expression for neuropathologic ranking. A history of TBI was associated with a significant increase in the DNA readers ZBTB4 and MeCP2 (p < 0.05) and a decrease in NSUN6 (p < 0.001) mRNA. These findings implicate regulation of protein pathways disrupted in AD and TBI via multiple pre- and post-transcriptional mechanisms including potentially acting upon transfer RNAs, enhancer RNAs as well as nuclear-cytoplasmic shuttling and cytoplasmic translational control. The targeting of such processes provides new therapeutic avenues for neurodegenerative brain conditions.

Journal Article Type Article
Acceptance Date Dec 23, 2022
Online Publication Date Jan 17, 2023
Publication Date Jan 17, 2023
Deposit Date Jan 27, 2023
Publicly Available Date Jan 31, 2023
Journal Molecular Neurobiology
Print ISSN 0893-7648
Electronic ISSN 1559-1182
Publisher Springer Science and Business Media LLC
Peer Reviewed Peer Reviewed
Keywords Neuroscience (miscellaneous); Cellular and Molecular Neuroscience; Neurology
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