Biology subjects

Guitart, T.

Publications and source records attributed to Guitart, T..

3 recordsLinked to original sources

bioRxiv2025

CSDE1 regulates miR-20a-5p/ TMBIM6 axis in melanoma

RNA-binding proteins (RBPs) and microRNAs (miRNAs) play crucial roles in regulating gene expression at the post-transcriptional level in tumorigenesis. They primarily target the 3'UTRs of mRNAs to control their translation and stability. However, their co-regulatory effects on specific mRNAs in the pathogenesis of particular cancers are yet to be fully explored. CSDE1 is an RBP that promotes melanoma metastasis, and the mechanisms underlying its function in melanoma development are yet to be fully understood. In the current study, we report that CSDE1 enhances TMBIM6 protein expression without altering its mRNA levels in melanoma cells, indicating post-transcriptional regulation. CSDE1 and AGO2 competitively bind to TMBIM6 mRNA, and we identify miR-20-5p, which represses TMBIM6 expression, regulates the binding of CSDE1 to TMBIM6 mRNA. Further, the RNA-binding mutant of CSDE1 foregoes its competitive binding to the mRNA, allowing AGO2-mediated silencing of TMBIM6 expression. Our study highlights the pivotal role of CSDE1 in regulating miR-20a-5p function and the expression of TMBIM6 in melanoma cells, thus unveiling the potential of therapeutic strategies targeting this regulatory pathway in treating malignant skin cancers.

molecular biology↗

bioRxiv2024

The Drosophila RNA binding protein Hrp48 binds a specificRNA sequence of the msl-2 mRNA 3' UTR to regulatetranslation

Repression of msl-2 mRNA translation is essential for viability of Drosophila melanogaster females to prevent hypertranscription of both X chromosomes. This translational control event is coordinated by the female-specific protein Sex-lethal (Sxl) which recruits the RNA binding proteins Unr and Hrp48 to the 3 untranslated region (UTR) of the msl-2 transcript and represses translation initiation. The mechanism exerted by Hrp48 during translation repression and its interaction with msl-2 are not well understood. Here we investigate the RNA binding specificity and affinity of the tandem RNA recognition motifs of Hrp48. Using NMR spectroscopy, molecular dynamics simulations and isothermal titration calorimetry, we identified the exact region of msl-2 3 UTR recognized by Hrp48. Additional biophysical experiments and translation assays give further insights into complex formation of Hrp48, Unr, Sxl and RNA. Our results show that Hrp48 binds independent of Sxl and Unr downstream of the E and F binding sites of Sxl and Unr to msl-2.

biophysics↗

bioRxiv2021

Ataxin-2, Twenty-four and Dicer-2 are components of a non-canonical cytoplasmic polyadenylation complex

Cytoplasmic polyadenylation is a mechanism to promote mRNA translation in a wide variety of biological contexts. A canonical complex centered around the conserved RNA-binding protein family CPEB has been shown to be responsible for this process. We have previously reported evidence for an alternative non-canonical, CPEB-independent complex in Drosophila, of which the RNA-interference factor Dicer-2 is a component. Here, we investigate Dicer-2 mRNA targets and protein co-factors in cytoplasmic polyadenylation. Using RIP-Seq analysis we identify hundreds of novel Dicer-2 target transcripts, [~]50% of which were previously found as targets of the cytoplasmic poly(A) polymerase Wispy, suggesting widespread roles of Dicer-2 in cytoplasmic polyadenylation. Large-scale immunoprecipitation revealed Ataxin-2 and Twenty-four among the high-confidence interactors of Dicer-2. Functional analysis indicate that both factors form an RNA-independent complex with Dicer-2, and are required for cytoplasmic polyadenylation of Dicer-2 targets. Our results reveal the composition of a novel cytoplasmic polyadenylation complex that operates during Drosophila early embryogenesis.

molecular biology↗