Nuclear-cytoplasmic translocation of MCIDAS couples transcription with massive de novo centriole biogenesis in multiciliated cells

Nuclear-cytoplasmic translocation of MCIDAS couples transcription with massive de novo centriole biogenesis in multiciliated cells

Cell Reports

10.1016/j.celrep.2025.116321

https://doi.org/10.1016/j.celrep.2025.116321

Hao Lu, Kim Jee Goh, Ee Kim Tan, Cameron T. James, Arnab Ghosh, Amélie-Rose Boudjema, Paolo Alberto Lorenzini, Colin D. Bingle, Sebastian Maurer-Stroh, Nidhan K. Biswas, Alice Meunier, N. Ray Dunn, Sudipto Roy

Cell Biology

23 September 2025

Lu, H., Goh, K. J., Tan, E. K., James, C. T., Ghosh, A., Boudjema, A.-R., Lorenzini, P. A., Bingle, C. D., Maurer-Stroh, S., Biswas, N. K., Meunier, A., Dunn, N. R., & Roy, S. (2025). Nuclear-cytoplasmic translocation of MCIDAS couples transcription with massive de novo centriole biogenesis in multiciliated cells. Cell Reports, 44(10), 116321. https://doi.org/10.1016/j.celrep.2025.116321

Multiciliated cells (MCCs) bear numerous motile cilia that drive fluid flow, but how numerous centrioles for multiciliation are generated has remained unresolved. Here, we report that the “master” MCC transcriptional regulator, MCIDAS, moonlights in the cytoplasm to organize massive centriole biogenesis. Like MCIDAS, its co-transcriptional factors, E2F4 and E2F5, also undergo cytoplasmic accumulation, colocalizing with MCIDAS and forming procentrioles. MCIDAS loss inhibited E2F4/5 cytoplasmic accumulation and blocked centriole assembly. Furthermore, we show that the cytoplasmic accumulation of MCIDAS is mediated by CRM1-dependant nuclear export, and its inhibition specifically compromised centriole biogenesis. By contrast, on loss of parental centrioles and deuterosomes, which does not impair centriole formation, E2F4 cytoplasmic localization remained unaffected, establishing that the MCIDAS-E2F4/5 cytoplasmic complex represents the de novo centriole biogenesis pathway. We have also assembled a comprehensive list of MCIDAS targets, a resource which will enable further exposition of MCC biology and pathological mechanisms of motile ciliopathies.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the National Medical Research Council - Open Fund - Individual Research Grant
Grant Reference no. : OFIRG19nov-0037

©2025 The Author(s). Published by Elsevier Inc. 1 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

https://oar.a-star.edu.sg/communities-collections/articles/22866

2211-1247

Institute of Molecular and Cell Biology