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

The prevailing model of microRNA function is that the "seed region" (nt 2-8) is 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 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 allele in which the 5' half of the mature microRNA retains its wild-type sequence, but the 3' half's sequence has been altered to robustly disrupt predicted pairing to this latter region. 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 -null mice. Our results indicate that 3' pairing is dispensable for the established myeloid function of this key mammalian microRNA.