Morgunova, V., Kobelyatskaya, A.A., Erokhin, M., Sokolova, O., Sizova, T.V., Kwon, D.A., Kalmykova, A. (2025). RNA-binding protein Ars2 mediates transcriptional silencing of telomeric repeats and transposable elements in the Drosophila germline.  Nucleic Acids Res. 53(10): gkaf486.

FBrf0262498

Research paper

Telomeres ensure genome stability and the levels of telomeric RNA reflect the integrity of telomeric chromatin. The highly conserved RNA-binding protein Ars2 (Arsenite-resistance protein 2) plays an essential role in the RNA nuclear metabolism and negatively regulates the expression of telomeric transcripts in human cells and in Drosophila. We found that germline knockdown of Drosophila Ars2 does not affect small RNA abundance but causes overexpression of telomeric repeats and transposable elements (TEs), accompanied by chromatin decompaction of these regions. The expression of a transgene containing the HeT-A telomeric retrotransposon was also affected by Ars2 knockdown. The mutation of the G-rich region, which is prone to the formation of G-quadruplex structures, reduces the HeT-A transgene's sensitivity to Ars2 depletion. Intriguingly, Ars2-regulated non-telomeric TEs are also enriched by G-quadruplex structures, implying their role in the Ars2 target recognition. Ars2 also prevents the formation of R-loops at telomeres, which are most likely caused by the accumulation of unreleased transcripts. Surprisingly, Ars2 is required for the expression of R1 retrotransposons, which are integrated in rRNA genes and essential for their amplification. Our findings point to a new mechanism for control of expression of telomeric repeats and TEs in the germline involving Ars2.

PMC12123415 (PMC) (EuropePMC)