# Functional analysis of mammalian midbody RNA in post-mitotic signaling functions

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $470,697

## Abstract

SUMMARY
The last step in cell division, abscission, relies on a transient structure called the midbody, which resides inside
the intercellular bridge between newly forming daughter cells. It consists of overlapping spindle midzone
microtubules which are coated with electron dense material called the midbody matrix. Long conceptualized as
a structural remnant subject to degradation following cytokinesis, emerging data suggest that midbodies play
instructive post-mitotic roles in establishing cell fate, proliferation state, tissue polarity, cilia formation, neuron
function, and oncogenesis. However, very little is known about the functional significance of the electron dense
material, since it was first actively pursued by Michael Mullins and Dick McIntosh in the 1970s, and then by
Ryoko Kuriyama in the 1980s. My lab has uncovered a surprising novel function for this electron dense material
in that it is a site of RNA storage and is a novel actively translating RNP granule with a uniquely complex life
cycle comprised of both membrane-less and membrane-bound phases, that we are calling the MB-granule (for
Midbody-granule). Employing quantitative, super-resolution approaches in live and fixed cells, coupled with
genomics and genetic manipulations to address our questions, we discovered that translation occurs in a
compartment surrounding the midbody RNP granule, as well as in post-mitotic midbody remnants (or MBRs),
and internalized MBRs (or MBsomes). RNA-seq data of isolated mammalian midbodies revealed an enrichment
of both oncogenic and stem cell transcription factors that have no described function in cell division, but
presumably act post-mitotically. Midbody-enriched transcripts initiate translation immediately before abscission,
a step that we have shown occurs in early G1, just after the nuclear envelope is fully reassembled. Treatments
commonly used to determine RNP phase condensates revealed that the midbody matrix behaves as a novel
type of RNP granule, and that the critical cytokinesis kinesin motor, Kif23/MKLP1, may serve as a novel RNP
scaffold. The MB-granule is a very novel class of RNP granule in that it’s translationally active, has membrane-
less and membrane-bound phases, and functions post-mitotically in cell fate and proliferative decisions. Here,
we will focus our efforts to determine the cell-type specific components of MBRs, the spatiotemporal regulation
of MBsome structure, and function, and if MB-granule RNAs are being liberated in cells that engulf them. Our
proposed studies will uncover unique insights into conserved and divergent MBsome structure and function,
offering insight into how this unique RNP condensate and organelle behaves as novel form of intercellular
communication.

## Key facts

- **NIH application ID:** 10489751
- **Project number:** 5R01GM139695-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Ahna Renee Skop
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $470,697
- **Award type:** 5
- **Project period:** 2021-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489751

## Citation

> US National Institutes of Health, RePORTER application 10489751, Functional analysis of mammalian midbody RNA in post-mitotic signaling functions (5R01GM139695-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10489751. Licensed CC0.

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