MiR-146a wild-type 3’ sequence identity is dispensable for proper innate immune function in vivo

Abstract

The prevailing model of microRNA function is that the \"seed\" region (nucleotides 2-8) is typically sufficient to mediate target recognition and repression. However, numerous recent studies have challenged this model, either by demonstrating extensive 3 pairing between physically defined miRNA-mRNA pairs or by showing in C. elegans that disrupted 3 pairing can result in impaired function in vivo. To test the importance of miRNA 3 pairing in a mammalian system in vivo, we engineered a mutant murine mir-146a allele in which the 5 half of the mature microRNA retains its wild-type sequence, but the 3 half has been altered to be anti-complementary. Mice homozygous or hemizygous for this mutant allele are phenotypically indistinguishable from wild-type controls and do not recapitulate any of the immunopathology previously described for mir-146a-null mice. Our results indicate that 3 pairing is dispensable for the established myeloid function of this key mammalian microRNA.\n\nSummary Blurb3 sequence identity is dispensable for the established function of a mammalian miRNA in vivo.