MiRNA function during early vertebrate development

Abstract

microRNAs (miRNAs) are short non-coding RNAs that down-regulate gene expression by pairing with sequences in the 3’UTR of target mRNAs. They play critical roles in diverse developmental and physiological events but the exact function of most miRNAs remains to be elucidated. Identification of bona fide targets is challenging due to partial base pairing between miRNAs and target 3’UTRs. To understand miRNA function during early vertebrate development, I first analyzed the general rules for miRNA:mRNA base pairing. By comparing the silencing ability of different miRNA recognition sites, I show that combinations of weak binding sites are just as effective as perfect sites for miRNA function. In addition, I uncovered a novel tissue-inductive role for miR-92 during early zebrafish development. Most previous work has focused on control of a number of cancer-related genes by miR-92, but here, using gain-of-function, loss-of-function, target identification, and genetic epistasis experiments, I demonstrate that miR-92 also regulates transcription factor gata5 and that such regulation is essential for proper endoderm formation and left-right patterning in zebrafish.