Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

RNA helicases are fundamental ATP-dependent enzymes that remodel RNA structures and ribonucleoprotein complexes. Recent studies reveal that RNA helicases are critical regulators of circular RNA networks, where circRNAs function as stable regulators of gene expression with important implications in disease. This study integrates structural, mechanistic, and functional insights into how RNA helicase families regulate circRNA biogenesis, stability, and function. Accumulating evidence demonstrates that RNA helicases can suppress circRNA biogenesis by remodeling intronic structures, such as DHX9 suppression, or promote biogenesis through DDX5/DDX17, which resolve inhibitory intronic structures by recruiting splicing factors (QKI, SRSF1) and stabilizing spliceosome assembly. We also highlight helicase-mediated control of circRNA stability and decay, such as EIF4A3, DDX5, and DDX17 protecting circRNAs from degradation by blocking decay factors, as well as reciprocal regulation in which circRNAs scaffold to modulate translation. In this review, we summarize RNA helicase families structures and circRNA biogenesis mechanisms, explore their extensive roles in circRNA regulation, and propose RNA helicases as central regulators and promising therapeutic targets, offering new avenues for biomarker development and RNA-based therapies.

Innate immunity is a multilevel system, where each stage plays a key role in ensuring effective immune defense. At the level of chromatin, transcription factors and coactivator protein complexes play a significant role in regulating the immune response. Here, we demonstrate that the conserved transcriptional coactivator SAYP, a component of the Brahma chromatin remodeling complex participates in the immune response of Drosophila melanogaster. Using immunoprecipitation, we detected an interaction between SAYP and the transcription factor DEAF1 and localized the domains within these proteins that mediate their association. Our data show that SAYP and DEAF1 are recruited to various regions of antimicrobial peptide genes in a gene- and pathogen-specific manner following an immune challenge by Escherichia coli or Micrococcus luteus in S2 cell culture. SAYP knockdown significantly reduces the activation of multiple antimicrobial peptide (AMP) genes, whereas DEAF1 knockdown has a more limited effect. In vivo analysis revealed that loss of full SAYP activity in a hypomorphic mutant significantly impairs the induction of several AMP genes in response to Escherichia coli infection. Furthermore, we found that SAYP cooperates with Relish and DEAF1 in some regulatory regions of antimicrobial genes. Consistently, flies harboring a hypomorphic SAYP mutation exhibited reduced survival following infection by Gram-positive and Gram-negative bacteria. Overall, these findings reveal that SAYP participates in a complex regulatory mechanism with Relish and DEAF1 that controls the innate immune response at the molecular and organismal levels.

Epigenetic marks induced by the environment play a key role in phenotypic plasticity and stress tolerance. We examined phenotypic responses in European sea bass D. labrax following a two-week exposure to fresh water (FW). FW transfer resulted in two distinct tolerance phenotypes: a tolerant (FWt) and an intolerant (FWi) group. FWi showed severe ion imbalance and pronounced stress. Using a genome-wide approach, we compared gill transcriptomic and DNA methylation profiles between phenotypes. RNA-seq analysis identified 7953 differentially expressed genes. Although ion transport pathways were not significantly altered, FWi showed profoundly modulated expression of genes involved in protein synthesis and quality control. These changes were associated with enhanced metabolic and biosynthetic processes, likely reflecting active gill remodelling under osmotic stress. In contrast, genes involved in tissue integrity, epithelial barrier function, and cell adhesion were downregulated. DNA methylation analysis revealed 5320 differentially methylated regions (DMRs) between phenotypes, with over 80% hypomethylated in FWi, suggestive of accelerated biological aging. Hypomethylation in promoters and first exons/introns was mainly linked to genes involved in cell structure and cell-cell interactions. Concordant hypomethylation and upregulation were observed for genes involved in the sphingolipid pathway, cytoskeleton organization, and cell signalling. Downregulated, hypermethylated genes were associated with GTPase activity and immune defence. Overall, our results exclude gill dysfunction as the cause of osmoregulatory failure. However, they also suggest that FW exposure may accelerate aging and reduce lifespan in FWi, potentially due to reduced plasticity and/or genetic variability.