An RFX transcription factor regulates ciliogenesis in the closest living relatives of animals

Maxwell C Coyle; Adia M Tajima; Fredrick Leon; Semil P Choksi; Ally Yang; Sarah Espinoza; Timothy R Hughes; Jeremy F Reiter; David S Booth; Nicole King

doi:10.1016/j.cub.2023.07.022

An RFX transcription factor regulates ciliogenesis in the closest living relatives of animals

Curr Biol. 2023 Sep 11;33(17):3747-3758.e9. doi: 10.1016/j.cub.2023.07.022. Epub 2023 Aug 7.

Authors

Affiliations

¹ Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
² Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
³ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
⁴ Donnelly Centre for Cellular and Biomolecular Research, Toronto, M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, M5S 3E1, Canada.
⁵ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁶ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁷ Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: nking@berkeley.edu.

Abstract

Cilia allowed our protistan ancestors to sense and explore their environment, avoid predation, and capture bacterial prey.¹^,²^,³ Regulated ciliogenesis was likely critical for early animal evolution,²^,⁴^,⁵^,⁶ and in modern animals, deploying cilia in the right cells at the right time is crucial for development and physiology. Two transcription factors, RFX and FoxJ1, coordinate ciliogenesis in animals⁷^,⁸^,⁹ but are absent from the genomes of many other ciliated eukaryotes, raising the question of how the regulation of ciliogenesis in animals evolved.¹⁰^,¹¹ By comparing the genomes of animals with those of their closest living relatives, the choanoflagellates, we found that the genome of their last common ancestor encoded at least three RFX paralogs and a FoxJ1 homolog. Disruption of the RFX homolog cRFXa in the model choanoflagellate Salpingoeca rosetta resulted in delayed cell proliferation and aberrant ciliogenesis, marked by the collapse and resorption of nascent cilia. In cRFXa mutants, ciliogenesis genes and foxJ1 were significantly downregulated. Moreover, the promoters of S. rosetta ciliary genes are enriched for DNA motifs matching those bound by the cRFXa protein in vitro. These findings suggest that an ancestral cRFXa homolog coordinated ciliogenesis in the progenitors of animals and choanoflagellates and that the selective deployment of the RFX regulatory module may have been necessary to differentiate ciliated from non-ciliated cell types during early animal evolution.

Keywords: FoxJ1; RFX; animal origins; choanoflagellate; cilia; ciliogenesis; evolution; transcription factor.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cilia / metabolism
DNA-Binding Proteins* / metabolism
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism
Gene Expression Regulation
Promoter Regions, Genetic
Regulatory Factor X Transcription Factors / genetics
Regulatory Factor X Transcription Factors / metabolism
Transcription Factors* / metabolism

Substances

Transcription Factors
DNA-Binding Proteins
Regulatory Factor X Transcription Factors
Forkhead Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding