Biology subjects

Tocchini, C.

Publications and source records attributed to Tocchini, C..

4 recordsLinked to original sources

bioRxiv2026

Safeguarding epithelial junctions by a novel quality control pathway

Cell junctions establish and maintain epithelial architecture despite fluctuating environmental and developmental conditions. A central question is how cells respond to challenging conditions to preserve junctional integrity. Here, we report the discovery of a previously unrecognized quality control pathway that monitors epithelial junctions (J-QC). We used the (I)Caenorhabditis elegans(/I) epidermis as a model to investigate the DLG-1-AJM-1 complex (DAC), a junctional domain that is critical for embryonic morphogenesis. We identify two mechanisms that sustain junctional integrity: first, localized (I)dlg-1(/I) mRNA ensures appropriate DLG-1 protein levels at the junction; repositioning (I)dlg-1(/I) RNA reduces DLG-1 levels, leading to gaps between epithelial cells. Second, transcription of DAC components responds to perturbations that disrupt the DAC. This response is sequence-independent, distinguishing it from other quality control mechanisms. It is activated by perturbations of the DAC or cytoskeleton and requires the LINC complex component ZYG-12/HOOK1-3 to transduce information about junctional integrity to the nucleus. These findings define a novel junctional QC for epithelial maintenance.

cell biology↗

bioRxiv2025

A short conserved sequence in the HOT region of the C. elegans dlg-1 gene largely recapitulates its transcriptional behavior during embryogenesis

High occupancy target (HOT) regions, genomic sites bound by many transcription factors, are found across eukaryotes, but their physiological roles remain unclear. We characterized two HOT regions in the Caenorhabditis elegans dlg-1 locus containing transcription start sites: one upstream the coding sequence and one in the first intron. The upstream region is essential for proper transcription and proper animal development, while the intronic region modestly enhances transcription in epidermal cells. Our findings reveal the functions of HOT regions in animal development, expanding the repertoire of gene regulation strategies in C. elegans.

genetics↗

bioRxiv2023

An adapted MS2-MCP system to visualize endogenous cytoplasmic mRNA with live imaging in Caenorhabditis elegans

Live imaging of RNA molecules constitutes an invaluable means to track the dynamics of mRNAs, but live imaging in Caenorhabditis elegans has been difficult to achieve. Endogenous transcripts have been observed in nuclei, but endogenous mRNAs have not been detected in the cytoplasm, and functional mRNAs have not been generated. Here, we have adapted live imaging methods to visualize mRNA in embryonic epithelial cells. We have tagged endogenous transcripts with MS2 hairpins in the 3 Untranslated Region (UTR) and visualized them after adjusting MS2 Coat Protein (MCP) expression. A reduced number of these transcripts accumulate in the cytoplasm, leading to loss-of-function phenotypes. In addition, mRNAs for dlg-1 fail to associate with the adherens junction, as observed for the endogenous mRNA. These defects are reversed by inactivating the nonsense-mediated decay pathway. RNA accumulates in the cytoplasm, dlg-1 associates with the adherens junction, and mutant phenotypes are rescued. These data suggest that MS2 repeats can induce the degradation of endogenous targets and alter the cytoplasmic distribution. Although our focus is RNAs expressed in epithelial cells during morphogenesis, this method can likely be applied to other cell types and stages. Summary statementAn adapted MS2-MCP method to tag endogenous transcripts in C. elegans embryos for live imaging without affecting mRNA stability.

genetics↗

bioRxiv2021

Translation-dependent mRNA localization to Caenorhabditis elegans adherens junctions

mRNA localization is an evolutionarily widespread phenomenon that facilitates sub-cellular protein targeting. Extensive work has focused on mRNA targeting through "zip codes" within untranslated regions (UTRs), while much less is known about translation-dependent cues. Here, we examine mRNA localization in Caenorhabditis elegans embryonic epithelia. From an smFISH-based survey, we identified mRNAs associated with the cell membrane or cortex, and with apical junctions in a stage- and cell type-specific manner. Mutational analyses for one of these transcripts, dlg-1/discs large, revealed that it relied on a translation-dependent process and did not require its 5 or 3 UTR. We suggest a model in which dlg-1 transcripts are co-translationally colocalized with the encoded protein: first the translating complex goes to the cell membrane through sequences of the SH3 domain, and then to the apical junction by the L27 and PDZ sequences. In addition, the Hook and GuK sequences contribute to the second step: they are required for mRNA, but not protein, to accumulate at the apical junctions from locations at or near the membrane. These studies identify a translation-based process for mRNA localization within developing epithelia and determine the necessary cis-acting sequences for dlg-1 mRNA targeting. Summary statementAn smFISH-based survey identified a subset of mRNAs coding for junctional components that localize at or in the proximity of the adherent junction through a translation-dependent mechanism.

developmental biology↗