Every great star has a sidekick who sometimes threatens to steal the show: Batman had Robin, Sherlock Holmes had Dr. Watson, and Hillary had Bill. Likewise, some proteins appear to have an intron-encoded miRNA sidekick that neutralizes the “bad guys” so that the protein can effectively perform its cellular function, as demonstrated in a recent NAR paper by Sailen Barik at the University of South Alabama.
Approximately 40% of mammalian miRNA sequences map within introns of protein-coding genes, but in most cases the relationship between the miRNA and the host gene is unknown. The precursor sequence for miR-338 lies within the eighth intron of the apoptosis-associated tyrosine kinase (AATK) gene. After transcription of AATK, a protein involved in neuronal differentiation, splicing and miRNA processing release mature miR-338.
Barik used search programs to identify potential mRNA targets of miR-338 and then showed that the translation of five predicted targets was inhibited by miR-388 in neurons. The five mRNA targets encoded antagonists of neuronal differentiation. Therefore, the intronic miR-338 assists its host gene by silencing multiple genes that are functionally antagonistic to AATK. Check out Nucleic Acids Research, October 2008 for the full story.