A study from Boston University Chobanian & Avedisian School of Medicine reports that transposable elements (TEs) are expressed in the human brain as large RNAs and processed into small RNAs (18–32 nucleotides). The findings provide insights into normal brain aging and neurodegenerative disorders.
TEs constitute about 40-50% of the human genome and are typically silenced by cellular defense mechanisms. In normal human brains from adolescence to adulthood, expression of large RNA messages from TEs increases, and a portion is processed into small RNA.
Key Findings
- In normal human brains from adolescence to adulthood, expression of large RNA messages from TEs increases, and a portion is processed into small RNA.
- The study analyzed brain samples from patients with Huntington's disease and Parkinson's disease.
- Huntington's disease was associated with altered small RNA expression from TEs; Parkinson's disease had a stronger impact on large RNAs from TEs.
- The researchers argue that TE RNA expression changes with age and processing from large to small RNA may help distinguish origins of neurodegenerative disorders.
Methods
The team used publicly available datasets from the NIH BrainSpan Atlas consortium and datasets generated by researchers at Boston University. The datasets included matched large and small RNA sequences from human brain samples. Bioinformatic analysis identified trends in TE RNA levels.
Researcher Commentary
"Transposons are usually silenced by our cells' genome defense mechanisms, but we find that normal human brains developing from adolescence to adults will naturally express more large RNA messages from transposons, and then the brain cells will metabolize some proportion into small RNA through either active or passive mechanisms."
— Nelson Lau, PhD, corresponding author
"We asked if transposon RNA expression in these two disease states could shed some light on the molecular differences between these two disorders. Since most studies ignore transposon RNAs, we want to bring back the attention to these more challenging transcripts to understand how our brains express and metabolize and handle these RNAs during aging."
— Nelson Lau, PhD
Funding
The study was funded by National Institutes of Health grants (R01GM135215, R01AR078306, R01AG078930, R01AG052465, R00AG063896, R35GM151127, R01NS073947).
The findings were published online in the journal Genome Research.