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bioRxiv · 10.1101/740753

Trading Genome Vulnerability for Stable Genetic Inheritance: Active Retrotransposons Help Maintain Pericentromeric Heterochromatin Required for Faithful Cell Division

Hao, Y.·Wang, D.·Wu, S.·Li, X.·Shao, C.·Zhang, P.·Chen, J.-Y.·Lim, D.-H.·Fu, X.-D.·He, S.·Chen, R.
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Abstract

Retrotransposons are extensively populated in vertebrate genomes, which, when active, are thought to cause genome instability with potential benefit to genome evolution. Retrotransposon-derived RNAs are also known to give rise to small endo-siRNAs to help maintain heterochromatin at their sites of transcription; however, as not all heterochromatic regions are equally active in transcription, it remains unclear how heterochromatin is maintained across the genome. Here, we attack these problems by defining the origins of repeat-derived RNAs and their specific chromatin registers in Drosophila S2 cells. We demonstrate that repeat RNAs are predominantly derived from active Gypsy elements, and upon their processing by Dicer-2, these endo-siRNAs act in cis and trans to help maintain pericentromeric heterochromatin. Remarkably, we show that synthetic repeat-derived siRNAs are sufficient to rescue Dicer-2 deficiency-induced defects in heterochromatin formation in interphase and chromosome segregation during mitosis, thus demonstrating that active retrotransposons are actually required for stable genetic inheritance.

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Hao, Y., Wang, D., Wu, S., Li, X., Shao, C., Zhang, P., Chen, J.-Y., Lim, D.-H., Fu, X.-D., He, S., Chen, R.. 2019-08-20. Trading Genome Vulnerability for Stable Genetic Inheritance: Active Retrotransposons Help Maintain Pericentromeric Heterochromatin Required for Faithful Cell Division. https://doi.org/10.1101/740753

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