PAF1 Knockdown May Reduce Age-Related Transposon Activation in Flies

There is a growing interest in the role of transposable elements, or transposons, in degenerative aging. Transposons are sequences in the genome capable of abusing genomic machinery in order to replicate themselves, thought to be the remnants of ancient viral activity. Their activity is repressed in youth, but those repression mechanisms are degraded by aging, as is true for near all systems in our cells. Rising transposon activity may contribute to dysfunction in all of the ways we might expect for genomic disruption, altering gene expression in cells throughout the body. Thus ways to prevent transposon activity are presently under investigation.

Transposable elements, also called transposons, are genetic parasites found in all animal genomes. Normally, transposons are compacted away in silent chromatin in young animals. But, as animals age and transposon-silencing defense mechanisms break down, transposon RNAs accumulate to significant levels in old animals like fruit flies. An open question is whether the increased levels of transposon RNAs in older animals also correspond to increased genomic copies of transposons.

This study approached this question by sequencing the whole genomes of young and old wild-type and mutant flies lacking a functional RNA interference (RNAi) pathway, which naturally silences transposon RNAs. Although the wild-type flies with intact RNAi activity had little new accumulation of transposon copies, the sequencing approach was able to detect several transposon accumulation occurrences in some RNAi mutants. In addition, we found that some fly transposon families can also accumulate as extra-chromosomal circular DNA copies.

Lastly, we showed that genetically augmenting the expression of RNAi factors can counteract the rising transposon RNA levels in aging and promote longevity. We show that knocking down PAF1, a conserved transcription elongation factor that antagonizes RNAi pathways, may bolster suppression of TEs during aging and extend lifespan. Our study suggests that in addition to a possible influence by different genetic backgrounds, small RNA and RNAi mechanisms may mitigate genomic transposon expansion despite the increase in transposon RNA transcripts during aging.


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