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PubMed2026

A CqbZIP55-CqPIF3 regulatory module associated with light-responsive flavonoid biosynthesis during quinoa seedling de-etiolation.

Quinoa (Chenopodium quinoa) is an emerging leafy vegetable and microgreen crop rich in health-promoting flavonoids, yet the regulatory mechanisms linking light perception to early metabolic adaptation remain unclear. Here, we integrated phenotypic, transcriptomic, metabolomic, and molecular analyses to investigate early de-etiolation responses in quinoa seedlings. Short-term light exposure rapidly promoted seedling establishment and induced transcriptional programs associated with photosynthesis, carbon metabolism, hormone signaling, and flavonoid biosynthetic gene expression, whereas metabolite changes were more limited, indicating temporal uncoupling between transcriptional activation and metabolic accumulation. Genome-wide bZIP analysis identified CqbZIP55 as a light-responsive regulator that directly binds and activates the CqCHS promoter. CqPIF3 also bound the CqCHS promoter and showed stronger transactivation activity than CqbZIP55 in transient reporter assays. Protein interaction and dual-luciferase assays showed that CqbZIP55 physically interacts with CqPIF3 and modulates CqPIF3-associated promoter activity. Exogenous quercetin upregulated CqbZIP55 and prolonged CqCHS expression, suggesting a candidate metabolite-associated reinforcement mechanism. Together, these findings support functional interplay between CqbZIP55 and CqPIF3 in light-responsive regulation of flavonoid biosynthetic gene expression in quinoa seedlings, while further quinoa-based perturbation and in vivo promoter-occupancy assays are required to establish their physiological role in planta. This study provides a framework for further investigation of photoprotective metabolic regulation in quinoa.

Chenopodium quinoa↗

PubMed2026

The pseudouridine epitranscriptomic landscape of advanced prostate cancer therapeutic resistance identifies TIMM17A as a key player.

BACKGROUND: Resistance to androgen receptor signaling inhibitors (ARSIs) remains a major barrier of advanced prostate cancer (PCa) treatment. While RNA epitranscriptomic modifications are increasingly recognized as key regulators of tumor biology, the role of pseudouridine (Ψ) in therapeutic resistance is largely unexplored. METHODS: A darolutamide-resistant PCa cell model was established and subjected to integrated multi-omics profiling using bulk RNA sequencing and photo-crosslinking-assisted Ψ sequencing (PA-Ψ-seq). Differential expression and pseudouridylation analyses were combined to identify Ψ-associated genes. Public datasets validated expression and prognosis. Functional assays including RNA knockdown, cell proliferation, colony formation, and xenograft models were conducted. Single-cell RNA sequencing investigated tumor microenvironment (TME) interactions. RESULTS: We identified extensive transcriptomic and pseudouridylation alterations associated with ARSI resistance, with a significant positive correlation between Ψ modification and mRNA expression. Integrated analysis highlighted a subset of "hyper-up" genes enriched in resistance-related pathways. Thus, TIMM17A was identified as a novel candidate. TIMM17A expression was significantly elevated in PCa and correlated with disease progression and poor prognosis. Experimental validations demonstrated that TIMM17A promoted tumor growth and resistance, while its knockdown restored sensitivity to darolutamide both in vitro and in vivo. Mechanistically, TIMM17A expression may be regulated by PUS1‑mediated pseudouridylation. Single-cell analysis further revealed that TIMM17A is enriched in malignant epithelial cells and associated with enhanced cell-cell communication within the TME. CONCLUSIONS: This study delineates the pseudouridine epitranscriptomic landscape in advanced PCa and identifies TIMM17A as a key mediator of therapeutic resistance. Targeting the Ψ-TIMM17A axis may offer a novel strategy to overcome ARSI resistance.

Advanced prostate cancer↗