Biology subjects

Zanin, O.

Publications and source records attributed to Zanin, O..

2 recordsLinked to original sources

bioRxiv2025

The RNA binding protein Insulin Growth factor 2 binding Protein 3 (IGF2BP3) modulates IL-13/IL-4 signalling in human bronchial epithelial cells and is dysregulated in type 2 disease

Type 2 immunity encompasses the coordinated cellular responses mainly driven by IL-4 and IL-13 to target extracellular parasites. Uncontrolled, type 2 responses underpin asthma and allergy. At the cellular level, IL-13 and IL-4 bind to receptors IL-13R1 and IL-4R and trigger STAT6 phosphorylation leading to the transcription of type 2 mediators. Further regulators of this fundamental pathway remain poorly understood. We demonstrate that the RNA binding protein Insulin Growth Factor 2 Binding Protein 3 (IGF2BP3) inhibits IL-13/IL-4 effects in airway epithelium and is increased in type 2 pathology, where it correlates with an IL-13-driven signature. Mechanistically, IGF2BP3 directly binds IL4R and IL13RA1 mRNAs, which are also methylated. Depleting IGF2BP3 increased IL4R and IL13RA1 mRNAs half-life, IL-4R and IL-13R1 surface expression and IL-13/IL-4-dependent STAT6 phosphorylation. Reducing IGF2BP3 levels skewed primary airway epithelial cells towards a type 2 phenotype and enhanced IL-13-mediated transcriptional effects genome-wide. Lastly, we found IGF2BP3 levels upregulated in airway epithelium in several type 2 disease cohorts, and an IGF2BP3-dependent IL-13-driven signature predominant in type 2 high vs type 2 low asthma. Our data positions IGF2BP3 as a novel inhibitor of IL-13/IL-4 effects and type 2 disease biomarker.

molecular biology↗

bioRxiv2022

Ceg1 depletion reveals mechanisms governing degradation of non-capped RNAs

Most functional eukaryotic mRNAs contain a 7-methylguanosine (m7G) cap which serves as a platform that recruits proteins to support essential biological functions such as mRNA processing, nuclear export and translation. Although capping is accomplished during the first steps of transcription the fate and turnover of uncapped transcripts have not been studied extensively. Here, we employed fast nuclear depletion of the capping enzymes in Saccharomyces cerevisiae to uncover the turnover of the transcripts that failed to be capped. We show that the levels of non-capped mRNAs are determined principally by the abundance of their synthesis. Nuclear depletion of the capping enzymes increases the levels of lowly expressed mRNAs and decreases mRNAs that are highly transcribed altogether mimicking the effects observed in cells lacking the predominantly cytoplasmic 5-3 exonuclease Xrn1. The nuclear 5-3 exonuclease Rat1 is not involved in the degradation of cap-defective transcripts and the lack of the capping does not affect the distribution of RNA Polymerase II on the chromatin. Our data indicate that the mRNAs that failed to be capped are not directed to a specific quality-control pathway and that the 5 cap role is associated with the Xrn1-dependent buffering of the cellular mRNA levels, along with protecting from 5-3 degradation.

molecular biology↗