MicroRNAs are short RNA molecules that do not encode for proteins but rather regulate the production of proteins from messenger RNAs. Importantly, microRNAs have been implicated in a broad range of stem cell roles in both healthy and diseased tissues. MicroRNAs show great promise as both biomarkers and therapeutics for disease. Interesting, there is increasing evidence for other classes of short RNA molecules of potentially equal importance. Here, we uncover members of other classes of short RNAs and show for the first time their functional relevance by dissecting their roles in the mammalian brain. Interestingly, we also find that these brain short RNAs are rapidly evolving suggesting they may underlie some of the functional differences between mouse and human brains.