Ancient RNA expression profiles from the extinct woolly mammoth

Ancient DNA has revolutionized the study of extinct and extant organisms that lived up to 2 million years ago, enabling the reconstruction of genomes from multiple extinct species, as well as the ecosystems where they once thrived. However, current DNA sequencing techniques alone cannot directly provide insights into tissue identity, gene expression dynamics, or transcriptional regulation, as these are encoded in the RNA fraction. Here, we report transcriptional profiles from 10 Late Pleistocene woolly mammoths. One of these, dated to be ∼39,000 years old, yielded sufficient detail to recover tissue-specific regulatory mechanisms and biological functions essential for skeletal muscle metabolism, representing the oldest ancient RNA sequences recorded to date. We showcase the potential to study ancient RNA molecules beyond preconceived limitations, providing an analytical framework for validating and decoding preserved transcriptomes through time. With our findings, we anticipate the emergence of integrative paleo-studies combining genomics, proteomics, and transcriptomics.