Argonaute 1 associates with nucleolar snoRNP machinery and regulates pre-rRNA levels and cell growth
- 1Hannover Medical School
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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BibTeX
@misc{hebalkar2026argonaute,
title = {{Argonaute 1 associates with nucleolar snoRNP machinery and regulates pre-rRNA levels and cell growth}},
author = {R. Hebalkar and N. Schumann and A. Yatsenko and R. J. Loureiro and K. Gresova and S. Guenzel and P. Alexiou and M. Seiler and J. M. Bujnicki and H. R. Shcherbata},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.759891},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.759891v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Argonaute 1 associates with nucleolar snoRNP machinery and regulates pre-rRNA levels and cell growth
AU - R. Hebalkar
AU - N. Schumann
AU - A. Yatsenko
AU - R. J. Loureiro
AU - K. Gresova
AU - S. Guenzel
AU - P. Alexiou
AU - M. Seiler
AU - J. M. Bujnicki
AU - H. R. Shcherbata
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.759891
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.759891v1
AB - 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.
ER -