Epitranscriptomics in poultry: RNA modifications as emerging regulators of growth, immunity, and metabolism: a narrative review

Epitranscriptomics has recently emerged as a dynamic layer of gene expression regulation, in which chemical modifications in RNA molecules, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), pseudouridine (Ψ), and 2′-O-methylation, modulate RNA stability, splicing, translation efficiency, and cellular responses to environmental stimuli. Although researchers have characterized >170 distinct RNA modifications across a broad range of organisms, the biological significance of these epitranscriptomic marks in birds remains largely unknown. This knowledge gap is especially important given the global economic impact of poultry production and the need to understand the molecular mechanisms that regulate growth efficiency, metabolic adaptation, immune competence, and disease resistance in chickens and other poultry species. Recent technological advances, notably nanopore direct RNA sequencing, enable direct analysis of native RNA molecules while preserving modification-associated signal patterns and avoiding reverse-transcription and amplification biases. However, the accuracy and resolution of modification detection depend on the modification type, sequencing chemistry, analytical model, read coverage, and availability of appropriate controls, and therefore often require orthogonal validation. These advances, especially in combination with integrative multi-omics approaches, provide unprecedented opportunities to map tissue-specific and condition-dependent epitranscriptomic landscapes in poultry. Here, we summarize the current knowledge of RNA modification mechanisms, review the available technologies for their detection with a focus on their application in poultry research, and critically evaluate emerging evidence that RNA modifications regulate muscle development, nutrient sensing, metabolic homeostasis, and innate and adaptive immunity. We then review the translational potential of epitranscriptomics for precision poultry nutrition, marker-assisted breeding programs, and novel disease control strategies, and identify key knowledge gaps and future research priorities. This review aims to bridge the gap between molecular understanding and practical application and provides a framework for incorporating epitranscriptomics into poultry science and sustainable livestock production.