Argonaute 1 associates with nucleolar snoRNP machinery and regulates pre-rRNA levels and cell growth

Hebalkar, R.; Schumann, N.; Yatsenko, A.; Loureiro, R. J.; Gresova, K.; Guenzel, S.; Alexiou, P.; Seiler, M.; Bujnicki, J. M.; Shcherbata, H. R.

doi:10.64898/2026.10.19.759891

bioRxiv · 10.64898/2026.10.19.759891

Argonaute 1 associates with nucleolar snoRNP machinery and regulates pre-rRNA levels and cell growth

Hebalkar, R.·Schumann, N.·Yatsenko, A.·Loureiro, R. J.·Gresova, K.·Guenzel, S.·Alexiou, P.·Seiler, M.·Bujnicki, J. M.·Shcherbata, H. R.

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Abstract

Argonaute proteins are best known as cytoplasmic effectors of small-RNA-mediated gene silencing, although their compartment-specific functions remain incompletely understood. Here, we identify a previously unrecognized nucleolar role for Drosophila Argonaute 1 (AGO1). We observed stress-induced redistribution of AGO1 into cytoplasmic and nuclear ribonucleoprotein assemblies, whereas a distinct AGO1 pool consistently localized to Fibrillarin-positive nucleoli. Co-immunoprecipitation further showed that AGO1 associates with Fibrillarin-containing complexes in vivo. Re-analysis of AGO1-associated small-RNA sequencing data revealed snoRNAs, particularly C/D box snoRNAs, among AGO1-bound RNA species and increased snoRNA representation following AGO1 overexpression. Structural modelling demonstrated that simultaneous molecular interaction of AGO1 and the Fibrillarin-containing snoRNP machinery with the same snoRNA is stereochemically feasible, providing a structural framework for their potential association within a nucleolar snoRNP assembly. Functionally, AGO1 depletion reduced pre-rRNA levels and decreased both nucleolar and cell size in the follicular epithelium. Depletion of Dicer-1 did not reproduce these growth defects, arguing against a general consequence of impaired miRNA biogenesis. Together, these findings identify AGO1 as a nucleolar regulator that associates with snoRNP machinery and links small-RNA biology to pre-rRNA homeostasis and cell growth.

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Hebalkar, R., Schumann, N., Yatsenko, A., Loureiro, R. J., Gresova, K., Guenzel, S., Alexiou, P., Seiler, M., Bujnicki, J. M., Shcherbata, H. R.. 2026-10-20. Argonaute 1 associates with nucleolar snoRNP machinery and regulates pre-rRNA levels and cell growth. https://doi.org/10.64898/2026.10.19.759891

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