C19MC Drives Nucleolar Invasion of Mitochondria and Meiotic Nuclear Division in Human Cancers

Overview

Journal iScience

Publisher Cell Press

Date 2024 Nov 20

PMID 39563898

Authors

Goodwin G Jinesh

Marian T Smallin

Nino Mtchedlidze

Marco Napoli

John H Lockhart

Elsa R Flores

Andrew S Brohl

Affiliations

Soon will be listed here.

Abstract

The chromosome-19 miRNA cluster (C19MC) restricts viruses depending on the multinucleated state of placental trophoblasts. However, the relationship of C19MC to multinucleation is unknown. Here we show that C19MC is coexpressed in multiple cancer type subsets with meiosis-related genes. We discovered a novel meiosis-III that exhibits simultaneous progression of meiotic nuclear division (MND) and cytokinesis. C19MC promotes meiotic bridged-chromosomes to block MND and cytokinesis to generate multinucleated cells. MND starts with the invagination of nuclear membrane to form nucle(ol)ar invasive cytoplasm (NiC), mitochondria and protein cargoes. Aurora-B regulates the efflux of cargos from NiC, whereas C19MC, CDK1, and autophagy promote cargo influx to inflate NiC size for MND progression. Using CRISPR human genetic engineering we demonstrate that the C19MC expression is required for NiC-driven MND and multinucleation. This discovery has impacts on cancer-pathogen interactions, immunotherapy, vertical transmission of viruses, antiviral research and SpCas9-CRISPR therapeutics.

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