Transposable element small RNAs and large RNAs in aging brains and implications in Huntington's and Parkinson's disease.

Gargi Dayama, Jou-Hsuan Roxie Lee, Shruti Gupta, Christian Brion, Brianne K Connizzo, Adam T Labadorf, Richard H Myers, Nelson C Lau

Department of Biochemistry and Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 02118, USA.Department of Biochemistry and Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts 02118, USA. · pubmed

Paper

Abstract

Transposable elements (TEs) are implicated in aging and neurodegenerative disorders, but the impact on brain TE RNA dynamics in these phenomena is not fully understood. Therefore, we quantify TE RNA changes in aging postmortem human and mouse brains and in the neurodegenerative disorders Huntington's disease (HD) and Parkinson's disease (PD). We track TE small RNAs (smRNAs) to assess the relationship to TE large RNA (laRNA) expression patterns. Human brain transcriptomes from the BrainSpan Atlas display significant shifts of TE smRNA patterns, whereas aging mouse brains lack any TE RNA changes despite a clear shift in aging-associated gene messenger RNA (mRNA) levels. The human frontal cortex displays the most pronounced sense TE smRNAs with a negative relationship between the TE smRNAs and laRNAs indicative of age-associated regulatory effects. Our analysis reveals TE smRNA dysregulation in HD, whereas PD shows a stronger impact on TE laRNAs, potentially correlating with the early average age of death for HD relative to PD. Furthermore, the TE-silencing factor

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Research summary

The paper claims that transposable element small RNAs (smRNAs) and large RNAs (laRNAs) exhibit significant dysregulation in aging brains and neurodegenerative diseases. The research investigates the dynamics of TE RNAs in the context of aging and neurodegeneration, which aligns with understanding the molecular mechanisms underlying aging and age-related diseases.

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