Scientists once thought transposable elements — stretches of DNA that can copy and move within the genome — were mostly silent in adult brains. A new Boston University study shows they’re surprisingly active, and their activity shifts in key ways during aging and neurodegeneration.
Nearly half the human genome is made up of sequences called transposable elements, or TEs — sometimes nicknamed “jumping genes” because of their ability to move or replicate within the genome. For decades, scientists largely dismissed them as genetic noise. But a new study from Boston University Chobanian & Avedisian School of Medicine is adding to a growing body of evidence that TEs play a meaningful role in brain health, aging and potentially the development of devastating neurological conditions like Huntington’s and Parkinson’s diseases.
The research, published May 28 in the journal Genome Research, reveals that transposable elements are not merely dormant passengers in our DNA. Instead, they are actively transcribed in human brain tissue throughout a person’s life — and the way those transcripts are processed changes as we age and shifts in distinctive ways depending on the disease.
From Silence to Signal
In healthy cells, genome defense mechanisms typically keep TEs suppressed. But the BU team found that as the human brain matures from adolescence into adulthood, it naturally begins producing more large RNA molecules derived from transposons. Brain cells then convert a portion of those large RNAs into small RNAs — sequences just 18 to 32 nucleotides long — through either active or passive molecular processes.
“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,” corresponding author Nelson Lau, an associate professor of biochemistry and director of the BU Genome Science Institute, said in a news release.
This large-to-small RNA conversion appears to be a normal feature of brain aging — one that hadn’t been systematically characterized until now. Understanding this baseline is critical, the researchers argue, because deviations from it may serve as molecular fingerprints for different neurological disorders.
Different Diseases, Different Disruptions
To investigate how neurodegeneration alters these patterns, Lau and his team analyzed brain tissue samples from patients who had Huntington’s disease and Parkinson’s disease — two of the most studied but still poorly understood conditions in neurology.
The results were striking in their specificity. Huntington’s disease was found to primarily affect the small RNA output from transposons, while Parkinson’s disease exerted a stronger influence on the large RNA transcripts. This divergence is scientifically significant because Huntington’s has a well-defined genetic cause — a repeating mutation in a single gene — while the origins of Parkinson’s remain far less clear.
“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,” Lau added.
The distinct molecular signatures could eventually help researchers trace Parkinson’s origins, or develop new diagnostic markers that identify the disease at an earlier stage — before symptoms become debilitating.
How the Study Was Conducted
The research team drew on two major types of datasets to build their analysis. The first came from the publicly available NIH BrainSpan Atlas consortium, a large resource that maps gene expression across the human brain at different developmental stages. The second consisted of unique datasets generated by the Richard Myers and Adam Labadorf research group at Boston University Chobanian & Avedisian School of Medicine.
What made these datasets especially valuable was that each human brain sample contained matched sets of both large and small RNAs — both sequenced from the same tissue. That pairing is relatively rare and allowed the team to track the relationship between the two RNA classes in the same biological context. The BU researchers then fed all of this data into a sophisticated bioinformatics analysis platform designed to identify trends in transposon RNA levels across aging and disease states.
Why It Matters for Students and Young People
Neurodegenerative diseases tend to be thought of as conditions that affect older adults, but the molecular processes underlying them begin far earlier in life. Huntington’s disease, for instance, can begin producing symptoms in a person’s 30s or 40s, and researchers believe the abnormal molecular environment may develop over years or even decades beforehand. Understanding how transposon RNA expression shifts from adolescence onward gives scientists a broader developmental window in which to search for early warning signs.
For students studying neuroscience, molecular biology, genetics or bioinformatics, this study also highlights a growing area of research that has been largely underexplored. Transposable elements make up roughly 40-50% of the human genome, yet the vast majority of brain RNA research focuses on protein-coding genes, which represent only a small fraction of our DNA. The study makes the case that the rest of the genome deserves far more attention.
The findings also underscore the power of large-scale bioinformatics — the computational tools used to analyze massive biological datasets — which is increasingly one of the most in-demand skill sets across both academia and the biotech industry.