Biology subjects

Palluzzi, F.

Publications and source records attributed to Palluzzi, F..

2 recordsLinked to original sources

bioRxiv2025

HnRNP C binding to inverted Alu elements protects the transcriptome from pre-mRNA circularization

Back-splicing is a non-canonical splicing event that drives the biogenesis of circular RNAs (circRNAs). Although the molecular mechanisms underlying circRNA biogenesis have been partially elucidated, how this process is globally regulated in tumors, has not been fully investigated. Herein, we uncover a hnRNP C-dependent mechanism that represses a broad repertoire of circRNAs in Group 3 medulloblastoma (MB). HnRNP C binds Alu elements and prevents the circularization of pre-mRNA transcripts. Expression of hnRNP C modulates the balance between linear and circular splicing and guarantees efficient expression of genes that sustain the oncogenic phenotype of Group 3 MB cells. Remarkably, in the absence of hnRNP C, the introns flanking the circularizing exons generate cytoplasmic dsRNAs through base-pairing of inverted Alu elements and trigger an interferon-induced antiviral response. These findings unveil the role of hnRNP C as guardian of transcriptome integrity by repressing circRNA biogenesis. Lastly, targeting hnRNP C in Group 3 MB may trigger an inflammatory immune response, thereby boosting cancer surveillance.

cancer biology↗

bioRxiv2021

Rescuing Biologically Relevant Consensus Regions Across Replicated Samples

MotivationProtein-DNA binding sites of ChIP-seq experiments are identified where the binding affinity is significant based on a given threshold. The choice of the threshold is a trade-off between conservative region identification and discarding weak, but true binding sites. ResultsWe argue the biological relevance of weak binding sites and the information they add when rescued. The sites are rescued using MSPC, which exploits replicates to lower the threshold required to identify a binding site while keeping a low false-positive rate. We extend MSPC to call consensus regions across any number of replicated samples, accounting for differences between biological and technical replicates. We observed several master transcription regulators (e.g., SP1 and GATA3) and HDAC2-GATA1 regulatory networks on rescued regions. Availability and implementationAn implementation of the proposed method and the scripts to reproduce the performed analysis are freely available at https://genometric.github.io/MSPC/, MSPC is distributed as a command-line application, an R package available from Bioconductor (https://doi.org/doi:10.18129/B9.bioc.rmspc), and a C# library.

bioinformatics↗