Alternative isoforms and phase separation of Ref1 repress morphogenesis in Cryptococcus.

Autor: Glueck NK; Department of Microbiology, University of Georgia, Athens, GA, USA., Xie X; Department of Microbiology, University of Georgia, Athens, GA, USA., Lin X; Department of Microbiology, University of Georgia, Athens, GA, USA. Electronic address: xiaorong.lin@uga.edu.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2024 Nov 26; Vol. 43 (11), pp. 114904. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1016/j.celrep.2024.114904
Abstrakt: Cryptococcus neoformans, the causative agent of cryptococcosis and a representative of the Basidiomycota phylum of Fungi, is a valuable model for our understanding of eukaryotic/fungal biology. Negative feedback is a well-documented mechanism across Eukarya to regulate developmental transitions. Here, we describe a repressor of the yeast-to-hypha transition, Ref1, which completes a negative feedback loop driven by the master regulator of hyphal morphogenesis, Znf2, during sexual development. Alternative transcription of Ref1, driven by Znf2, produces a functionally distinct Ref1 isoform. Isoform-specific capacity for phase separation imparts this functional distinction, making Ref1 a stronger repressor and more vulnerable to proteolytic degradation. The multimodal nature of Ref1 provides versatility that allows cells to fine-tune Ref1 activity to suit developmental context. This work reveals a mechanism by which phase separation allows a transcriptional program to tailor its own repression to guide an organism through morphological transition.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE