Coordinated microRNA-mRNA regulatory remodelling across the compressed maturation of the African killifish (Nothobranchius furzeri)

Abstract

The turquoise killifish (Nothobranchius furzeri) is an emerging vertebrate model for development and ageing due to its exceptionally rapid maturation and short lifespan. However, how microRNA (miRNA) regulation coordinates gene expression across its compressed developmental trajectory remains poorly understood. Here, we integrated miRNA and mRNA expression from the same unexposed animals across three developmental stages: newly hatched fry (4 weeks total age), juveniles (~8 weeks total age), and aged adults (~8 months of age). Developmental stage was the dominant source of variation in both datasets, with miRNA and mRNA profiles independently resolving a consistent progression from newly hatched fry to juveniles and adults. Transcriptomic changes reflected ongoing tissue maturation, including increased expression of crystallin genes associated with lens development, while more than 2,000 genes were differentially expressed during the juvenile transition. Integration of 398 developmentally dynamic miRNAs with predicted mRNA targets identified specific miRNAs whose developmental changes were significantly enriched for opposing changes in their target genes. These included conserved developmental regulators from the miR-200/141, miR-29, let-7, and miR-34 families, which increased toward adulthood as their predicted target cohorts decreased. Stage-controlled analyses further identified miR-34a, miR-29a, miR-29b, miR-15a, and a novel candidate whose target relationships persisted independently of the overall developmental trajectory. Notably, miR-29 showed particularly strong induction during maturation, consistent with its conserved roles in extracellular-matrix remodeling, differentiation, and vertebrate ageing. Together, these findings reveal coordinated remodeling of conserved miRNA-mRNA regulatory programs across the rapid maturation of N. furzeri and establish a framework for investigating post-transcriptional regulation during vertebrate development in a species with limited miRNA annotation.