Biology subjects

Bonnet-Madin, L.

Publications and source records attributed to Bonnet-Madin, L..

3 recordsLinked to original sources

bioRxiv2026

MacroH2A1 and H3K27me3 target cGAS to facultative heterochromatin to restrain innate immune activation

The DNA sensor cGAS is largely sequestered on chromatin in an inactive form, but how this state is regulated remains unclear. We show that cGAS preferentially binds nucleosomes containing the histone variant macroH2A1 (mH2A1) marked by H3K27me3 and H3K9me3. Cryo-EM reveals that cGAS selectively engages the mH2A1/H2B acidic patch within heterotypic nucleosomes. Depleting mH2A1.1 or blocking H3K27me3 deposition releases cGAS from chromatin and activates the cGAS-STING-IRF3 pathway. Genome-wide profiling reveals two cGAS-bound chromatin compartments: chromosome-arm sites co-occupied by mH2A1.1, methylated CpG islands, and CTCF, where cGAS and mH2A1.1 binding are interdependent; and centromeric regions (14% of peaks), which lack DNA methylation and mH2A1.1 dependence. These findings establish mH2A1 and H3K27me3 as determinants of cGAS chromatin tethering, linking nuclear cGAS regulation to facultative heterochromatin and opening new avenues for modulating cGAS-STING signaling.

cell biology↗

bioRxiv2021

RACK1 associates with RNA-binding proteins Vigilin and SERBP1 to control dengue virus replication

Dengue virus (DENV), a re-emerging virus transmitted by Aedes mosquitoes, causes severe pathogenesis in humans. No effective treatment is available against this virus. We recently identified the scaffold protein RACK1 as a component of the DENV replication complex, a macromolecular complex essential for viral genome amplification. Here, we show that RACK1 is important for DENV infection. RACK1 mediates DENV replication through binding to the 40S ribosomal subunit. Mass spectrometry analysis of RACK1 partners coupled to a loss-of-function screen identified the RNA binding proteins Vigilin and SERBP1 as DENV host dependency factors. Vigilin and SERBP1 interact with DENV viral RNA (vRNA), forming a ternary complex with RACK1 to mediate viral replication. Overall, our results indicate that RACK1 recruits Vigilin and SERBP1, linking the DENV vRNA to the translation machinery for optimal translation and replication.

microbiology↗

bioRxiv2021

Characterization and functional interrogation of SARS-CoV-2 RNA interactome

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has caused a devastating global health crisis. The emergence of highly transmissible novel viral strains that escape neutralizing responses emphasizes the urgent need to deepen our understanding of SARS-CoV-2 biology and to develop additional therapeutic strategies. Using a comprehensive identification of RNA binding proteins (RBP) by mass spectrometry (ChIRP-M/S) approach, we identified 142 high-confidence cellular factors that bind the SARS-CoV-2 viral genome during infection. By systematically knocking down their expression in a human lung epithelial cell line, we found that the majority of the RBPs identified in our study are proviral factors that regulate SARS-CoV-2 genome replication. We showed that some of these proteins represented drug targets of interest for inhibiting SARS-CoV-2 infection. In conclusion, this study provides a comprehensive view of the SARS-CoV-2 RNA interactome during infection and highlights candidates for host-centered antiviral therapies.

microbiology↗