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The midbody (MB) is a transient structure at the spindle midzone that is required for cytokinesis, the terminal stage of cell division. Long ignored as a vestigial remnant of cytokinesis, we now know MBs are released post-abscission as extracellular vesicles called MB remnants (MBRs) and can modulate cell proliferation, fate decisions, tissue polarity, neuronal architecture, and tumorigenic behavior. Here, we demonstrate that the MB matrix—the structurally amorphous MB core of unknown composition—is the site of ribonucleoprotein assembly and is enriched in mRNAs that encode proteins involved in cell fate, oncogenesis, and pluripotency, that we are calling the MB granule. Using a quantitative transcriptomic approach, we identified a population of mRNAs enriched in mitotic MBs and confirmed their presence in signaling MBR vesicles released by abscission. The MB granule is unique in that it is translationally active, contains both small and large ribosomal subunits, and has both membrane-less and membrane-bound states. Both MBs and post-abscission MBRs are sites of spatiotemporally regulated translation, which is initiated when nascent daughter cells re-enter G1 and continues after extracellular release. We demonstrate that the MB is the assembly site of an RNP granule. MKLP1 and ARC are necessary for the localization and translation of RNA in the MB dark zone, whereas ESCRT-III was necessary to maintain translation levels in the MB. Our data suggest a model in which the MB functions as a novel RNA-based organelle with a uniquely complex life cycle. We present a model in which the assembly and transfer of RNP complexes are central to post-mitotic MBR function and suggest the MBR serves as a novel mode of RNA-based intercellular communication with a defined biogenesis that is coupled to abscission, and inherently links cell division status with signaling capacity. To our knowledge, this is the first example of an autonomous extracellular vesicle with active translation activity.HighlightsThe MB, the center region of the intercellular bridge, is the assembly site of a ribonucleoprotein granule, we call the MB granuleDistinct oncogenic and pluripotent transcription factor RNAs, includingJun/FosandKLF4, are packaged in MBs and MBRsThe MB granule is coincident with the MB matrix, or dark zone, of the MBThe Kif23/MKLP1 kinesin is a core hexanediol-sensitive MB granule componentThe MB and MBR are site of active translation that begins in early G1 and continues post-mitoticallyMKLP1 and ARC are necessary for RNA targeting/maintenance and translation at the MBDepletion of ESCRT-III increases the levels of translation during abscissionAbscission releases MBRs as MB granule-harboring, translating extracellular vesiclesMultiple cell types including cancer, stem, neural stem, all have actively translating MBRsMBRs are proposed as a novel mode of intercellular communication by extracellular vesicle-mediated direct transfer of RNA |
