A5015450985- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Bacterial Genetics and Biotechnology
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- RNA regulation and disease
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Helicobacter pylori-related gastroenterology studies
- Advanced Power Generation Technologies
- Antimicrobial Resistance in Staphylococcus
- PI3K/AKT/mTOR signaling in cancer
- Genomics, phytochemicals, and oxidative stress
- Gut microbiota and health
- COVID-19 Clinical Research Studies
- Prostate Cancer Treatment and Research
- Coal Combustion and Slurry Processing
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
University of California, San Francisco
2019-2024
UCSF Helen Diller Family Comprehensive Cancer Center
2019-2024
Institut Curie
2023-2024
Inserm
2023-2024
Centre National de la Recherche Scientifique
2018-2024
Université Paris Sciences et Lettres
2024
Université Paris-Saclay
2024
Université Claude Bernard Lyon 1
2015-2020
Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
2015-2020
Institut de Biologie Physico-Chimique
2018
Post-transcriptional regulation of RNA stability is a key step in gene expression control. We describe regulatory program, mediated by the binding protein TARBP2, that controls nucleus. TARBP2 to pre-mRNAs results increased intron retention, subsequently leading targeted degradation TARBP2-bound transcripts. This recruitment m6A methylation machinery its target transcripts, where deposition marks influences splicing regulators, inhibiting efficient splicing. Interactions between and...
Abstract Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition complex behaviors are not well described. Here, we report bi-directional changes in depression-related after genetic disruption of neuronal cytosine methylation, including conditional ablation transgene-derived overexpression Nsun2 mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease m 5 C levels, resulting deficits expression 70% Gly isodecoders. Altogether,...
Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report systematic effort to decipher RNA structural code shapes pathological during breast cancer metastasis. We discovered previously unknown enhancer enriched near cassette exons with increased inclusion in highly metastatic cells. show spliceosomal protein small nuclear ribonucleoprotein polypeptide A' (SNRPA1) interacts these enhancers...
Abstract Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, address this, we used ribosome profiling compare genome-wide translation efficiencies and highly metastatic breast patient-derived xenografts. We developed dedicated regression-based methods analyse alternative...
Enterococcus faecalis is a commensal bacterium of the human intestine and major opportunistic pathogen in immunocompromised elderly patients. The pathogenesis E. infection relies part on its capacity to colonize gut. Following disruption intestinal homeostasis, can overgrow, cross barrier, enter lymph bloodstream. To identify characterize genes that are key colonization, our strategy consisted screening mutants for following phenotypes related lifestyle: antibiotic resistance, overgrowth,...
Abstract Antisense RNAs are ubiquitous in human cells, yet their role is largely unexplored. Here we profiled antisense the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one RNA that drives progression by upregulating redox enzyme NADPH quinone dehydrogenase 1 (NQO1), named it NQO1-AS. Knockdown of either NQO1 or NQO1-AS reduced colonization a mouse model, investigation into indicated broadly protective against oxidative damage ferroptosis....
Breast cancer's tendency to metastasize poses a critical barrier effective treatment, making it leading cause of mortality among women worldwide. A growing body evidence is showing that translational adaptation emerging as key mechanism enabling cancer cells thrive in the dynamic tumor microenvironment (TME). Here, we systematically summarize how breast utilize drive metastasis, highlighting intricate regulation by specific translation machinery and mRNA attributes such sequences structures,...
Abstract The No-Go Decay (NGD) mRNA surveillance pathway degrades mRNAs containing stacks of stalled ribosomes. Although an endoribonuclease has been proposed to initiate cleavages upstream the stall sequence, production two RNA fragments resulting from a unique cleavage never demonstrated. Here we use expressing 3′-ribozyme produce truncated transcripts in vivo mimic naturally occurring known trigger NGD. This technique allows us analyse endonucleolytic events at single-nucleotide...
Identifying master regulators that drive pathologic gene expression is a key challenge in precision oncology. Here, we have developed an analytic framework, named PRADA, identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes their target regulons. Application this approach to data collected from clinical samples, patient-derived xenografts, and cell line models colon cancer metastasis revealed protein RBMS1 as suppressor progression. We observed...
RNA structural switches are key regulators of gene expression in bacteria, but their characterization Metazoa remains limited. Here, we present SwitchSeeker, a comprehensive computational and experimental approach for systematic identification functional switches. We applied SwitchSeeker to the human transcriptome identified 245 putative To validate our approach, characterized previously unknown switch 3' untranslated region RORC (RAR-related orphan receptor C) transcript. In vivo dimethyl...
Transcriptome analyses have revealed that convergent gene transcription can produce many 3′-overlapping mRNAs in diverse organisms. Few studies examined the fate of 3′-complementary double-stranded RNA-dependent nuclear phenomena, and nothing is known about cytoplasmic destiny messengers or their impact on expression. Here, we demonstrate complementary tails interact cytoplasm promote post-transcriptional regulatory events including no-go decay (NGD) Saccharomyces cerevisiae. Genome-wide...
Activation of the PI3K-mTOR pathway is central to breast cancer pathogenesis including resistance many targeted therapies. The mTOR kinase forms two distinct complexes, mTORC1 and mTORC2, understanding which required for survival malignant cells has been limited by tools selectively completely impair either subcomplex. To address this, we used RMC-6272, a bi-steric molecule with rapamycin-like moiety linked an active-site inhibitor that displays >25-fold selectivity over mTORC2 substrates....
Small noncoding RNAs (smRNAs) play critical roles in regulating various cellular processes, including development, stress response, and disease pathogenesis. However, functional characterization of smRNAs remains limited by the scale simplicity phenotypic readouts. Recently, single-cell perturbation screening methods, which link CRISPR-mediated genetic perturbations to rich transcriptomic profiling, have emerged as foundational scalable approaches for understanding gene functions, mapping...
Transfer RNAs (tRNAs), once viewed as static adaptors in translation, are now recognized dynamic regulators of gene expression. While recent studies have illuminated roles for tRNA stability, the upstream mechanisms governing transcription remain poorly understood. To address this gap, we generated EXpression atlas (EXTRNA), a high-resolution expression dataset spanning 24 cell lines across 9 human tissues. EXTRNA revealed both tissue-type-specific programs ("tRNAomes") and unexpected...
Abstract From extrachromosomal DNA to neo-peptides, the broad reprogramming of cancer genome leads emergence molecules that are specific state. We recently described orphan non-coding RNAs (oncRNAs) as a class cancer-specific small with potential play functional roles in breast progression 1 . Here, we report systematic and comprehensive search identify, annotate, characterize cancer-emergent oncRNAs across 32 tumor types. also leverage large-scale vivo genetic screens xenografted mice...
Small non-coding RNAs can be secreted through a variety of mechanisms, including exosomal sorting, in small extracellular vesicles, and within lipoprotein complexes. However, the mechanisms that govern their sorting secretion are not well understood. Here, we present ExoGRU, machine learning model predicts RNA probabilities from primary sequences. We experimentally validated performance this ExoGRU-guided mutagenesis synthetic sequence analysis. Additionally, used ExoGRU to reveal cis trans...
Abstract Accurate quantification of transcript isoforms is crucial for understanding gene regulation, functional diversity, and cellular behavior. Existing RNA sequencing methods have significant limitations: short-read (SR) provides high depth but struggles with isoform deconvolution, whereas long-read (LR) offers resolution at the cost lower depth, higher noise, technical biases. Addressing this gap, we introduce Multi-Platform Aggregation Quantification Transcripts (MPAQT), a generative...
ABSTRACT RNA structural switches are key regulators of gene expression in bacteria, yet their characterization Metazoa remains limited. Here we present SwitchSeeker, a comprehensive computational and experimental approach for systematic identification functional switches. We applied SwitchSeeker to the human transcriptome identified 245 putative To validate our approach, characterized previously unknown switch 3’UTR RORC transcript. In vivo DMS-MaPseq, coupled with cryogenic electron...
Abstract Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major hub in oncogenesis, however its effects on cancer progression remain poorly understood. To address this, we used ribosome profiling compare genome-wide translation efficiencies and highly metastatic breast patient-derived xenografts. We developed novel regression-based methods analyze alternative...
Summary/Abstract The neural crest (NC) is highly multipotent and generates diverse lineages in the developing embryo. However, spatiotemporally distinct NC populations display differences fate potential, such as increased gliogenic parasympathetic potential from later migrating, nerve-associated Schwann cell precursors (SCPs). Interestingly, while melanogenic shared by both early migrating SCPs, melanocyte identity resulting differentiation through these temporally progenitors have not been...
Abstract The No-Go Decay (NGD) mRNA surveillance pathway degrades mRNAs containing stacks of stalled ribosomes. Although an endoribonuclease has been proposed to initiate cleavages upstream the stall sequence, production two RNA fragments resulting from a unique cleavage never demonstrated. We have used expressing 3’-ribozyme produce truncated transcripts in vivo mimic naturally occurring known trigger NGD. This technique allows us analyse endonucleolytic events at single-nucleotide...