A Transposable Element within the Non-canonical Telomerase RNA of Modulates Telomerase in Response to DNA Damage

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Telomerase is a highly regulated enzyme whose activity is essential for long-term cellular proliferation. In the presence of DNA double-strand breaks (DSBs), telomerase activity must be curtailed to promote faithful DNA repair. We previously showed that the flowering plant Arabidopsis thaliana rapidly down-regulates telomerase in response to DSBs, and further that this mode of regulation is dependent on TER2, a non-canonical telomerase RNA subunit. Here we demonstrate that the unique regulatory properties of TER2 are conveyed by a transposable element (TE) embedded in the TER2 gene. A comparison of A. thaliana accessions with and without the TE revealed that the element increases the binding affinity of TER2 for the telomerase catalytic subunit TERT relative to the canonical telomerase RNA subunit. The TE also increases TER2 turnover. In response to DSBs, TER2 is induced and accumulates in TERT containing complexes in vivo. Thus, invasion of a TE endows TER2 with a DNA damage sensor to rapidly and reversibly modulate enzyme activity in response to genotoxic stress. These findings provide an example of how exaptation of a TE altered the function of a long noncoding RNA. In this case, a duplicated gene (TER2) was used as the platform, and the TE as the tool to engineer a novel mode of telomerase regulation.

Vyšlo v časopise: A Transposable Element within the Non-canonical Telomerase RNA of Modulates Telomerase in Response to DNA Damage. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005281
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005281

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