bioRxiv Science⌕ Search

Biology subjects

Turchi, L.

Publications and source records attributed to Turchi, L..

3 recordsLinked to original sources

Plant-TFClass: a structural classification for plant transcription factors

Transcription factors (TFs) bind DNA at specific sequences to regulate gene expression. This universal process is achieved thanks to the DNA-binding domain (DBD) present in each TF. DBDs show a vast diversity of protein folds within and across organisms, ranging from simple long basic alpha helices to complex structural combinations of alpha, beta and loop folds. In mammals, the structural conformation of the DBDs and the way it establishes contact with DNA has been used to organize TFs in a hierarchical classification named TFClass. However, such classification is missing from plants that possess many DBD types absent from mammals. Here, we reviewed the numerous TF DBD 3D-structures and models available for plants to organize all plant TFs types following the TFClass hierarchy (Superclass/Class/Family/Subfamily). We classified most of the 55 recognized plant TF types within the existing TFClass framework. This extended classification led us to add six new classes and 34 new families corresponding to TF DBD structures absent in mammals. Plant-TFClass provides a unique resource for TF and TF binding sites comparison across TF families and across organisms.

plant biology↗

The F-box cofactor UFO redirects the LEAFY floral regulator to novel cis-elements

In angiosperms, flower patterning requires the localized expression of the APETALA3 (AP3) floral homeotic gene involved in petal and stamen development. AP3 is synergistically induced by the master transcription factor (TF) LEAFY (LFY) and the F-box protein UNUSUAL FLORAL ORGANS (UFO), but the molecular mechanism underlying this synergy has remained unknown. Here we show that the connection to ubiquitination pathways suggested by the F-box domain of UFO is mostly dispensable for its function and that UFO instead acts by forming a transcriptional complex with LFY and binds to newly discovered regulatory elements. Cryo-electron microscopy explains how a LFY-UFO complex forms on these novel DNA sites due to direct interaction of UFO with LFY and DNA. Finally, we show that this complex has a deep evolutionary origin, largely predating flowering plants. This work reveals a novel mechanism of an F-box protein in directly modulating the DNA-binding specificity of a master TF.

plant biology↗

Human glioblastoma cell motility depends on the activity of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase

Cancer cells in similar functional states are found in all glioblastoma, despite the genomic heterogeneity observed between and within these brain tumors. Metabolism being downstream of all signaling pathways regulating cell behaviors, we looked for metabolic weaknesses in link with motility, a key functional state for glioblastoma aggressiveness. A signature-driven data reduction approach highlighted motile cells present in thirty tumors from four independent single-cell transcriptomic datasets. Analyses integrating trajectory modeling disclosed, as characteristic of motile cells, enhanced oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). The soundness of this prediction was verified using migration and invasion assays with patient-derived cells and tissue organoids. Pharmacological and genetic manipulations showed that enhanced ROS production and MPST activity are required for the cells motility. Biochemical assays indicated that MPST acts by protecting protein cysteine residues from dismal hyperoxidation. In vivo, MPST knockdown translated in reduced tumor burden, and a robust increase in mice survival. These results show that enhanced oxidative stress coupled with MPST mobilization plays a key role in glioblastoma cell motility.

cancer biology↗