(Boston)—Transposable elements (TEs), also called transposons, are DNA sequences capable of moving or replicating from one location to another within a genome. While TEs are the most significant fraction of the human genome (approximately 40-50%), only recently have scientists begun to appreciate their impact impact on human diseases from cancer to neurodegenerative disorders.
Usually, our cells keep TEs quiet when we are young, but in a new study from Boston University Chobanian & Avedisian School of Medicine, researchers have discovered that TEs are actively expressed in human brains as large RNAs that can then be processed into small RNAs (18-32 nucleotides long). This finding provides new molecular insights into how our brains age normally, as well as how neurodegenerative disorders can impact these normal patterns of transposon RNA expression.
"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," explains corresponding author Nelson Lau, PhD, associate professor of biochemistry and director of the BU Genome Science Institute at the school.
Specifically, the researchers explored how this transposon RNA processing could be affected in brain samples from patients impacted by the neurodegenerative disorders of Huntington's and Parkinson's diseases. Their results showed that Huntington's disease impacts transposon small RNA expression and Parkinson's exerts a stronger impact on transposon large RNAs. The researchers argue that transposon RNA expression deserves more attention in neurodegenerative disorders because our brains continue to express transposon RNAs as we age, and the processing from the large RNA to small RNA could reveal the different origins of neurodegenerative disorders.
Lau and his team designed their study to access both publicly available datasets generated by the NIH BrainSpan Atlas consortium, as well as unique datasets made by the Richard Myers and Adam Labadorf group at Boston University Chobanian & Avedisian School of Medicine. These human brain RNA datasets are special for containing both a matched set of large RNAs with small RNAs that are both sequenced from each human sample. The BU team then combined all these datasets together in a complex bioinformatics analysis platform that looked for trends in the changes for transposon RNA levels.
According to the researchers, there is a distinct genetic cause to Huntington's Disease, but the genetic cause for Parkinson's Disease remains obscure. "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," adds Lau.
The findings appear online in the journal Genome Research.
N.C.L. was funded by National Institutes of Health (NIH) grants R01GM135215, R01AR078306, R01AG078930, and
R01AG052465. B.K.C. was funded by NIH grants R00AG063896 and R35GM151127. R.H.M. was funded by NIH grant R01NS073947.
