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

Argonaute 2 (AGO2) is an indispensable component of the RNA-induced silencing complex, operating at the transcriptional 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. Statement: AGO2 resides in open-ended tunneling nanotubes and close-ended cytokinetic bridges. At the latter location AGO2 colocalises with cell division components and the authors show that AGO2 deregulation impairs cell division fidelity.