Biology subjects

Rizzo, M.

Publications and source records attributed to Rizzo, M..

2 recordsLinked to original sources

bioRxiv2021

The SUMO protease Ulp2 regulates genome stability and drug resistance in the human fungal pathogen Candida albicans

Stress-induced genome instability in microbial organisms is emerging as a critical regulatory mechanism for driving rapid and reversible adaption to drastic environmental changes. In Candida albicans, a human fungal pathogen that causes life-threatening infections, genome plasticity confers increased virulence and antifungal drug resistance. Discovering the mechanisms regulating C. albicans genome plasticity is a priority to understand how this and other microbial pathogens establish life-threatening infections and develop resistance to antifungal drugs. We identified the SUMO protease Ulp2 as a critical regulator of C. albicans genome integrity through genetic screening. Deletion of ULP2 leads to hypersensitivity to genotoxic agents and increased genome instability. This increased genome diversity causes reduced fitness under standard laboratory growth conditions but enhances adaptation to stress, making ulp2{Delta}/{Delta} cells more likely to thrive in the presence of antifungal drugs. Whole-genome sequencing indicates that ulp2{Delta}/{Delta} cells counteract antifungal drug-induced stress by developing segmental aneuploidies of chromosome R and chromosome I. We demonstrate that intrachromosomal repetitive elements drive the formation of complex novel genotypes with adaptive power.

microbiology↗

bioRxiv2020

An Eutherian-Specific microRNA Controls the Translation of Satb2 in a Model of Cortical Differentiation

Cerebral cortical development is controlled by key transcription factors that specify the neuronal identities in the different cortical layers. These transcription factors are crucial for the identity of the different neurons, but the mechanisms controlling their expression in distinct cells are only partially known. Here we investigate the expression and stability of the mRNAs of Tbr1, Bcl11b, Fezf2, Satb2 and Cux1 in single developing mouse cortical cells. We focus on Satb2 and find that its mRNA expression occurs much earlier than its protein synthesis and in a set of cells broader than expected, suggesting an initially tight control of its translation, which is subsequently de-repressed at late developmental stages. Mechanistically, Satb2 3UTR modulates protein translation of GFP reporters during mouse corticogenesis. By in vitro pull-down of Satb2 3UTR-associated miRNAs, we select putative miRNAs responsible for SATB2 inhibition, focusing on those strongly expressed in early progenitor cells and reduced in late cells. miR-541, an Eutherian-specific miRNA, and miR-92a/b are the best candidates and their inactivation triggers robust and premature SATB2 translation in both mouse and human cortical cells. Our findings indicate that RNA interference plays a major role in the timing of cortical cell identity and may be part of the toolkit involved in specifying supra-granular projection neurons.

developmental biology↗