Ancient microRNA profiles of a 14,300-year-old canid are taxonomically informative and give glimpses into gene regulation from the Pleistocene

Ancient DNA sequencing is the key technology for paleogenomic studies and today a routine method in many laboratories. Recent analyses have shown that, under favoring conditions, also RNA can be sequenced from historical and even ancient samples. We have re-analyzed ancient RNA data from a Pleistocene canid and find - in addition to the previously described messenger RNA fragments - intact microRNAs, which are short transcripts with important gene regulatory functions. With an extraordinary age of 14,300 years, the canid microRNA profiles are the oldest ever reported. Despite their age, we show that the microRNA profiles are conclusive of taxonomic origin, tissue identity with organ- and cell-type specific signatures, and that they yield glimpses into gene regulatory activity and biological processes from the Pleistocene. In summary, we here show that straightforward microRNA analyses hold great promise for deeper insights into gene regulation in extinct animals.