Biology subjects

Ricci, B.

Publications and source records attributed to Ricci, B..

3 recordsLinked to original sources

bioRxiv2026

Single residues within the YTHDF intrinsically disordered region control m6A-dependent mRNA decay

Intrinsically disordered regions (IDRs) mediate protein interactions, condensate partitioning, and regulatory control in RNA-binding proteins, yet the residue-level logic underlying IDR function has remained difficult to define using conventional fragment- and truncation-based approaches. Here, we apply cytosine and adenine base-editor screens to map residue-level regulation within the intrinsically disordered region of YTHDF2, a cytoplasmic reader that couples m6A to mRNA decay. By tiling base edits across YTHDF2 in a YTHDF1/YTHDF3-null background, we identify IDR residues that regulate YTHDF2-dependent cellular fitness. Interestingly, we identified residues that limit YTHDF2 decay activity. Their mutation disrupts endogenous protein-protein interactions and generates hyperactive YTHDF2 variants that promote m6A-dependent mRNA decay and alter recruitment to cytoplasmic RNA granules, without affecting intrinsic m6A binding or protein stability. These findings define the residue-level regulatory logic of the YTHDF2 IDR and establish base-editor screening as a strategy to uncover functional mechanisms encoded within IDR regions.

systems biology↗

bioRxiv2024

YTHDC1 m6A-dependent and m6A-independent functions converge to preserve DNA damage response.

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 of its impact on a fully efficient DNA damage response remains limited. Here, through a targeted CRISPR-knockout screen, we identified RNA binding proteins and modifiers that participate in mediating the p53 response. Among the top hits, m6A reader YTHDC1 was identified as a master regulator of p53 expression. YTHDC1 binds to the transcription start sites of TP53 and other genes involved in DNA damage response, promoting their transcriptional elongation. YTHDC1 deficiency leads to reduced TP53 expression, and also retention of introns leading to aberrant protein production of key DNA damage factors. While intron retention is dependent on m6A, YTHDC1 favors TP53 transcriptional pause-release independently of m6A. Depletion of YTHDC1 causes genomic instability and aberrant cancer cell proliferation mediated by genes regulated by YTHDC1. Our results uncover YTHDC1 as an orchestrator of the DNA damage response through distinct mechanisms of co-transcriptional mRNA regulation.

cancer biology↗

bioRxiv2022

Converting cropping systems into seasonal habitat functionality reveals the hump-shaped responses of carabid beetles to agricultural management

O_LIUnderstanding effects on the huge diversity of cropping systems on local biodiversity is challenging but necessary to implement agroecological systems. Through a functional approach, the translation of cropping systems into resource and disturbance gradients is promising to decipher the relationship between cropping systems and biodiversity but has never been implemented for arthropods. C_LIO_LITo investigate contributions of resource and disturbance gradients arising from cropping systems vs environmental context (regional effect, meteorological conditions and landscape characteristics) on beneficial arthropod communities, we used a dataset collected in 60 crop fields from three French areas over a five-years period. It includes all farmers interventions, crop sequences, meteorological data, landscape composition and carabid samplings. C_LIO_LIWe found that the environmental context contributed to about 75% of explained carabid variations on average, while resource and disturbance gradients contributed to about 25% of explained carabid variations. The resource and disturbance gradients were particularly important in winter and spring preceding the spring-summer period to determine carabid variations. C_LIO_LIMoreover, we identified thresholds above which resource and disturbance gradients start being beneficial or detrimental for carabids. For example, a Treatment Frequency Index above 2.07 in spring decreased the total activity density of carabids during the spring-summer period. C_LIO_LISynthesis and application. While implementing for the first time a functional approach to understand the effects of different facets of cropping systems on arthropods, our study also allows us to identify periods and thresholds above which specific practices affect carabids. The identification of such thresholds can guide the provision of recommendations for policy, stakeholders and farmers about how to reduce cropping systems impact on arthropods. C_LI

ecology↗