SRP491025 PRJNA1079296 A male-essential microRNA is key for avian sex chromosome dosage compensation In birds, females have two different sex chromosomes (ZW) and males have two identical ones (ZZ). As birds evolved, the W chromosome lost many genes. It's been unclear how birds adjusted to this loss in females. We studied a Z-linked microRNA (miR-2954) highly expressed in males and thought to help balance gene expression. When we knocked out miR-2954 in chickens, male embryos died, because dosage-sensitive Z-linked genes were over-expressed in males. Our research shows that birds have developed a unique mechanism to balance gene expression between the sexes, with a miRNA crucial for male survival.