Biology subjects

Quevedo, L.

Publications and source records attributed to Quevedo, L..

3 recordsLinked to original sources

bioRxiv2025

Systemic resistance to pathogens in Arabidopsis requires HASTY-dependent miRNA cell-to-cell movement.

Plant defenses against pathogens are tightly regulated through complex gene expression control mechanisms. The precise activation and repression of defense-related genes are crucial to balancing the trade-off between growth and immunity. Micro RNAs (miRNAs) play a well-established role in the local regulation of plant-microbe interactions. While some miRNAs are also essential for systemic defense responses, their mechanisms of action, biogenesis, and long-distance mobility remain largely unexplored. Here, we show that HASTY (HST), a key factor in miRNA biogenesis and intercellular movement, is required for systemic defense activation. The impaired mobility of miRNAs in hst mutants correlates with a lack of systemic responses. In infected tissues, HST may enhance the co-transcriptional processing of specific pri-miRNAs, which promotes the cell-to-cell movement of their mature miRNAs and contributes to the activation of systemic defenses. Furthermore, two miRNAs that exhibit increased mobility during systemic defense induction are required for a proper systemic response. Interestingly, complementing hst mutants with a version of HST expressed exclusively in companion cells is sufficient to restore systemic defense induction, highlighting the role of miRNA cell-to-cell movement. These findings shed light on the role of HST in plant immunity, linking miRNA biogenesis and mobility to the fine-tuned regulation of systemic defenses.

molecular biology↗

bioRxiv2022

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, and enhances the viral infection of Burkitt lymphoma cells

The molecular hallmark of Burkitt lymphoma (BL) is a chromosomal translocation that results in deregulated expression of MYC oncogene. This translocation is present in virtually all BL. MYC is an oncogenic transcription factor deregulated in about half of total human tumors, by translocation or other mechanisms. Transcriptomic studies reveal more than 1000 genes regulated by MYC but a much smaller fraction of these genes is directly activated by MYC. All the endemic BL and many sporadic BL cells are associated to the Epstein-Barr virus (EBV) infection. The currently accepted mechanism for the MYC and BL association is that EBV is the causing agent inducing MYC translocation. Complement receptor 2 or CR2 (also called CD21) is a membrane protein that serves as EBV receptor in lymphoid cells. Here we show that CR2 is a direct MYC target gene. This conclusion is based on several evidences. First, MYC downregulation is linked to CR2 downregulation both in proliferating and in arrested cells. Second, MYC binds human CR2 promoter and this binding depends on E-box elements. Third, MYC activates CR2 promoter in an E-box dependent manner. Four, MYC activates CR2 transcription in the absence of protein synthesis. Importantly, MYC also induces CR2 expression in mouse primary B cells. Thus, CR2 is a bona fide MYC direct target gene. Moreover, higher MYC expression levels in Burkitt lymphoma-derived cells result in a more efficient EBV infection. We propose an alternative mechanism compatible with the correlation between EBV infection and MYC translocation observed in endemic BL, i.e., that deregulated MYC in BL cells occurs first and favors the EBV infection.

cancer biology↗

bioRxiv2020

ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to PARP inhibition in lung cancer

The survival rate in lung cancer remains stubbornly low and there is an urgent need for the identification of new therapeutic targets. Last decades research has evidenced a clear role of chromatin structure in cancer development and several members of the SWI/SNF chromatin remodeling complexes have been described altered in different tumor types. Nevertheless, the precise mechanisms of their impact on cancer progression, as well as the application of this knowledge to cancer patient management are largely unknown. In this study, we have performed targeted sequencing of a cohort of lung cancer patients on genes involved in chromatin structure, as well as functional experiments to identify the molecular mechanisms linking alterations of chromatin remodeling genes and tumor development. We have identified ARID2 production loss in 20% of lung cancer patients. Additionally, we have shown that ARID2-deficiency provokes profound chromatin structural changes, alters the transcriptional programme and impairs DNA repair which bolster the proliferative and metastatic potential of the cells both in vitro and in vivo. Moreover, we have demonstrated that ARID2 deficiency significantly affects the sensitivity of the cells to PARP inhibition. All these results support that ARID2 is a bona-fide tumor suppressor gene in lung cancer that might be exploited therapeutically.

cancer biology↗