AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division

Vasiliki I Pantazopoulou,Elias Chatzitheodoridis,Vicky Filippa,Ema Anastasiadou,Eleni Dragona,Stella Georgiou,Dimitris Thanos,Maja Thiele,Anastasios D Delis,Stamatis N Pagakis,Sofia Tseleni-Balafouta,Athanassios D Velentzas,Ismini Kloukina,Dimitrios J Stravopodis,Jonel Trebicka,Sarantis Gagos

doi:10.1038/s42003-021-02130-0

Abstract

Argonaute 2 (AGO2) is an indispensable component of the RNA-induced silencing complex, operating at the translational or posttranscriptional level. It is compartmentalized into structures such as GW- and P-bodies, stress granules and adherens junctions as well as the midbody. Here we show using immunofluorescence, image and bioinformatic analysis and cytogenetics that AGO2 also resides in membrane protrusions such as open- and close-ended tubes. The latter are cytokinetic bridges where AGO2 colocalizes at the midbody arms with cytoskeletal components such as α-Τubulin and Aurora B, and various kinases. AGO2, phosphorylated on serine 387, is located together with Dicer at the midbody ring in a manner dependent on p38 MAPK activity. We further show that AGO2 is stress sensitive and important to ensure the proper chromosome segregation and cytokinetic fidelity. We suggest that AGO2 is part of a regulatory mechanism triggered by cytokinetic stress to generate the appropriate micro-environment for local transcript homeostasis.

Highlights

Argonaute 2 (AGO2) is an indispensable component of the RNA-induced silencing complex, operating at the translational or posttranscriptional level
AGO2 resided in Actin-filopodial-like structures that are many per cell (Fig. 1a, b), and in tubular protrusions that are always formed in paired cells (Fig. 1a, c, d)
Immunofluorescence assays demonstrated that Drosha and DGCR8 exhibited punctuate expression patterns within both tunneling open- (Fig. 2a, b) and close-ended nanotubes (Fig. 2d, e), similar to those observed with AGO2

Summary

Introduction

Argonaute 2 (AGO2) is an indispensable component of the RNA-induced silencing complex, operating at the translational or posttranscriptional level. It is compartmentalized into structures such as GW- and P-bodies, stress granules and adherens junctions as well as the midbody. 1234567890():,; Argonaute (AGO) proteins are at the hub of RNA-induced silencing complex (RISC), a major contributor to the finetuning of gene expression due to posttranscriptional regulation[1]. There has been an association between RISC and endosomes at synapses, through the interaction of PICK1 and AGO2, and the relocalization of the latter to endosomal compartment This results in an elevated translation of mRNA targets locally[23], dictating the spatio-temporal homeostasis. Our results provide support for an AGO2 complex at the midzone, essential in cytokinesis and cell-division integrity

Methods

Results

Conclusion