Tuesday 25.11 13:00 CET we are happy to host Prof. Leon Schulte (rna-lab.org) @schultelab.bsky.social join us for an exciting talk "Multi-omic Dissection of Regulatory lncRNA-Protein Networks in Innate Immunity" thanks @rnasociety.bsky.social @imbb-forth.bsky.social us02web.zoom.us/meeting/regi...
Tuesday 25.11 13:00 CET we are happy to host Prof. Leon Schulte (rna-lab.org) @schultelab.bsky.social join us for an exciting talk "Multi-omic Dissection of Regulatory lncRNA-Protein Networks in Innate Immunity" thanks @rnasociety.bsky.social @imbb-forth.bsky.social us02web.zoom.us/meeting/regi...
upon genome-wide search for pvt1-like transcripts (expression levels, intron retention average across hundreds of samples, intronic miR-200 seed sites), and assessing splicing-based models for more candidates, PVT1 emerges as a top candidate with chromatin-associated, intron-retained ceRNA potential
Mechanistically, PVT1 contains several miR-200 seed sites, perfect 7-mers, located within its intronic regions; artificial splicing enhancement of PVT1 with dCasRx-RBM25 (doi.org/10.1016/j.molcel.2024.05.028) in MCF-7 reduced PVT1 intron retention and altered expression of miR-200 target genes (6/n)
Causal inference analysis using tumor-specific somatic mutations (WGS/WXS) clustered near PVT1 splice sites and associated with perturbed PVT1 splicing uncovers specific terms and miR-200 target genes enriched in datasets best explained by the causal model (among eight alternative models tested) 5/n
PVT1 has several alternative transcript isoforms detected in breast cancer samples (quantified with Salmon doi.org/10.1038/nmeth.4197), yet splicing-based predictive models outperform transcript-expression-based models in predicting distal gene expression (4/n)
We extracted splicing efficiency at PVT1 3' splice sites across hundreds of breast cancer data (TCGA) and built machine learning models to predict gene expression in genome-wide in silico screens; we find specific terms and miR-200/205 target genes enriched among high-confidence predicted genes (3/n
In previous work we measured chromatin dissociation dynamics of nascent RNAs, and profiled co- and post-transcriptional processing doi.org/10.1016/j.cels.2023.09.005; Here, we frame PVT1 as a chromatin-associated lncRNA with inefficient processing;
happy to share new preprint doi.org/10.1101/2025...; how does splicing-based processing of lncRNAs affect gene expression in cis or in trans, and shape distant regulatory networks?
Stop the doom scrolling! A new 🗞️ from my lab, describing one of our flagship projects of many years we are super excited to share:
"Inducible formation of fusion transcripts upregulates haploinsufficient CHD2 gene expression".
A 🧵
biorxiv.org/content/earl...
