DOI: 10.1101/474791Nov 20, 2018Paper

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

BioRxiv : the Preprint Server for Biology
Joel R NeilsonAndrew Grimson


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.

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