Biology subjects

Baptista, T.

Publications and source records attributed to Baptista, T..

3 recordsLinked to original sources

bioRxiv2026

A Mediator-dependent hypertranscriptional program governs neural stem cell fate decisions in vivo

Hypertranscription, a global increase in transcriptional output, is a defining feature of stem cells, but its biological relevance and regulation in vivo remain unclear. Using Drosophila neural stem cells (neuroblasts), we investigate the function and regulation of hypertranscription. Neuroblasts exhibit higher transcriptional activity than their differentiated progeny, establishing them as a model of hypertranscriptional stem cells. We identify the Mediator complex as a key regulator of this elevated transcriptional state. Mediator is broadly enriched across neuroblast chromatin, and its depletion causes a substantial, selective reduction in transcription in neuroblasts, with only mild effects in differentiated cells. Functionally, Mediator depletion impairs lineage progression, causing an accumulation of undifferentiated, stem-like cells, highlighting the necessity of hypertranscription for proper stem cell fate and differentiation. Finally, we show that Drosophila brain tumor neuroblasts exhibit an exaggerated, Mediator-dependent hypertranscriptional program. These findings establish Mediator as a central regulator of hypertranscription in both normal and tumorigenic neural stem cells, crucial for neural differentiation and stem cell fate progression.

developmental biology↗

bioRxiv2024

FLYNC: A Machine Learning-Driven Framework for Discovering Long Non-Coding RNAs in Drosophila melanogaster

Non-coding RNAs have increasingly recognized roles in critical molecular mechanisms of disease. However, the non-coding genome of Drosophila melanogaster, one of the most powerful disease model organisms, has been understudied. Here, we present FLYNC - FLY Non-Coding discovery and classification - a novel machine learning-based model that predicts the probability of a newly identified RNA transcript being a long non-coding RNA (lncRNA). Integrated into an end-to-end bioinformatics pipeline capable of processing single-cell or bulk RNA sequencing data, FLYNC outputs potential new non-coding RNA genes. FLYNC leverages large-scale genomic and transcriptomic datasets to identify patterns and features that distinguish non-coding genes from protein-coding genes, thereby facilitating lncRNA prediction. We demonstrate the application of FLYNC to publicly available Drosophila adult head bulk transcriptome and single-cell transcriptomic data from Drosophila neural stem cell lineages and identify several novel tissue- and cell-specific lncRNAs. We have further experimentally validated the existence of a set of FLYNC positive hits by qPCR. Overall, our findings demonstrate that FLYNC serves as a robust tool for identifying lncRNAs in Drosophila melanogaster, transcending current limitations in ncRNA identification and harnessing the potential of machine learning.

genomics↗

bioRxiv2017

Architecture of TAF11/TAF13/TBP complex suggests novel regulatory state in General Transcription Factor TFIID function

General transcription factor TFIID is a key component of RNA polymerase II transcription initiation. Human TFIID is a megadalton-sized complex comprising TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). TBP binds to core promoter DNA, recognizing the TATA-box. We identified a ternary complex formed by TBP and the histone fold (HF) domain-containing TFIID subunits TAF11 and TAF13. We demonstrate that TAF11/TAF13 competes for TBP binding with TATA-box DNA, and also with the N-terminal domain of TAF1 previously implicated in TATA-box mimicry. In an integrative approach combining crystal coordinates, biochemical analyses and data from cross-linking mass-spectrometry (CLMS), we determine the architecture of the TAF11/TAF13/TBP complex, revealing TAF11/TAF13 interaction with the DNA binding surface of TBP. We identify a highly conserved C-terminal TBP-binding domain (CTID) in TAF13 which is essential for supporting cell growth. Our results thus have implications for cellular TFIID assembly and suggest a novel regulatory state for TFIID function.

biochemistry↗