A5008569712- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Viral-associated cancers and disorders
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Nutrition, Genetics, and Disease
- Epigenetics and DNA Methylation
- NF-κB Signaling Pathways
- Genetic factors in colorectal cancer
- Identification and Quantification in Food
- HVDC Systems and Fault Protection
- Acute Myeloid Leukemia Research
- CRISPR and Genetic Engineering
- Peptidase Inhibition and Analysis
- Ferroptosis and cancer prognosis
Columbia University
2024
Columbia University Irving Medical Center
2024
Cornell University
2017-2023
University of Trento
2013-2021
University of Florence
2011
N6-methyladenosine (m6A) is the most abundant mRNA nucleotide modification and regulates critical aspects of cellular physiology differentiation. m6A thought to mediate its effects through a complex network interactions between different sites three functionally distinct cytoplasmic YTHDF m6A-binding proteins (DF1, DF2, DF3). In contrast prevailing model, we show that DF bind same m6A-modified mRNAs rather than mRNAs. Furthermore, find do not induce translation in HeLa cells. Instead,...
The tumor suppressor TP53 is the most frequently mutated gene product in human cancer. Close to half of all solid tumors carry inactivating mutations gene, while remaining cases, activity abrogated by other oncogenic events, such as hyperactivation its endogenous repressors MDM2 or MDM4. Despite identification hundreds genes regulated this transcription factor, it remains unclear which direct target and downstream pathways are essential for suppressive function TP53. We set out address...
YTHDF proteins bind the N6-methyladenosine (m6A)-modified mRNAs, influencing their processing, stability, and translation. Therefore, members of this protein family play crucial roles in gene regulation several physiological pathophysiological conditions. contain a hydrophobic pocket that accommodates m6A embedded RRACH consensus sequence on mRNAs. We exploited presence cage to set up an m6A-competitive assay performed high-throughput screen aimed at identifying ligands binding pocket....
Many recent studies using ChIP-seq approaches cross-referenced to trascriptome data and also potentially unbiased in vitro DNA binding selection experiments are detailing with increasing precision the p53-directed gene regulatory network that, nevertheless, is still expanding. However, most have been conducted established cell lines subjected specific p53-inducing stimuli, both factors biasing results. We developed p53retriever, a pattern search algorithm that maps p53 response elements...
N 6 -methyladenosine (m A) is the most prevalent modified nucleotide in mRNA, and it has important functions mRNA regulation. However, our understanding of specific m A along with its cytosolic readers, YTHDF proteins, changed substantially recent years. The original view was that different sites within an could have depending on which paralog bound to it, YTHDF1 inducing translation, while YTHDF2 induced degradation. As a result, each proposed unique physiologic roles arise from their...
Relatively few studies have examined the link between SNPs and mRNA translation, despite established importance of translational regulation in shaping cell phenotypes. We developed a pipeline analyzing allelic imbalance total polysome-bound mRNAs from paired RNA-seq data HCT116 cells identified 40 candidate tranSNPs, i.e. associated with allele-specific translation. Among them, SNP rs1053639 (T/A) on DNA damage-inducible transcript 4 (DDIT4) 3UTR was identified, reference T allele showing...
// Alessandra Bisio 1 , Judit Zámborszky 1, 3 Sara Zaccara Mattia Lion 4 Toma Tebaldi 2 Vasundhara Sharma Ivan Raimondi Federica Alessandrini Yari Ciribilli Alberto Inga Laboratory of Transcriptional Networks, Centre for Integrative Biology, CIBIO, University Trento, 38123, Italy Translational Genomics, Institute Enzymology, Research Natural Sciences, Budapest, Hungary Department Genetics, Massachusetts General Hospital, Boston, MA, USA Correspondence to: Ciribilli, e-mail:...
Activation of p53 by the small molecule Nutlin can result in a combination cell cycle arrest and apoptosis. The relative strength these events is difficult to predict classical gene expression analysis, leaving uncertainty as therapeutic benefits. In this study, we report translational control mechanism shaping p53-dependent Using polysome profiling, establish Nutlin-induced apoptosis associate with enhanced translation mRNAs carrying multiple copies an identified 3' UTR CG-rich motif...
Abstract Cells have evolved a robust and highly regulated DNA damage response to preserve their genomic integrity. Although increasing evidence highlights the relevance of RNA regulation, our understanding its impact on fully efficient remains limited. Here, through targeted CRISPR-knockout screen, we identify RNA-binding proteins modifiers that participate in p53 response. Among top hits, find m 6 A reader YTHDC1 as master regulator expression. binds transcription start sites TP53 other...
mRNAs are regulated by nucleotide modifications that influence their cellular fate. Two of the most abundant modified nucleotides N6-methyladenosine (m6A), found within mRNAs, and N6,2-O-dimethyladenosine (m6Am), which is at first-transcribed nucleotide. A long-standing challenge has been distinguishing these similar in transcriptome-wide mapping studies. Here we identify biochemically characterize, PCIF1, methyltransferase generates m6Am. We find PCIF1 binds dependent on m7G cap. By...
Cells have evolved a robust and highly regulated DNA damage response to preserve their genomic integrity. Although increasing evidence highlights the relevance of RNA regulation, our understanding its impact on fully efficient remains limited. Here, through targeted CRISPR-knockout screen, we identified binding proteins modifiers that participate in mediating p53 response. Among top hits, m6A reader YTHDC1 was as master regulator expression. binds transcription start sites TP53 other genes...
The search for mechanisms underlying different cellular responses to the treatment with Nutlin-3, an MDM2 inhibitor that unleashes p53, revealed a translational control mechanism involving RNA binding proteins PCBP2 and, particularly, DHX30. Sifting through multi-functional p53-dependent transcriptional output, this can modulate activation of cell death pathways.
Abstract Several genome-wide transcriptome analyses that focused on p53-induced cellular responses in many contexts have continued to expand the already vast p53-regulated transcriptional networks. To investigate post-transcriptional controls as an additional dimension of p53-directed gene expression we performed translatome analysis by polysomal profiling MCF7 cells treated with Doxorubicin and Nutlin-3a. A comparison between revealed a considerable level uncoupling, meaning genes whose...
Abstract The tumor suppressor p53 and NF-kB are sequence-specific transcription factors (TFs) playing crucial roles in controlling cell proliferation survival with an undeniable impact on cancer progression. In response to cellular stresses they induce the expression of a large variety genes. Synergistic or antagonistic interactions between proteins may modulate common targets potentially lead modified response. To specifically investigate cell-autonomous, cooperative gene changes, we...