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bioRxiv · 10.1101/474791

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

Neilson, J. R.·Bertolet, G.·Kongchan, N.·Miller, R.·Patel, R. K.·Jain, A.·Choi, J. M.·Saltzman, A.·Christenson, A.·Jung, S. Y.·Malovannaya, A.·Grimson, A.
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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.

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Neilson, J. R., Bertolet, G., Kongchan, N., Miller, R., Patel, R. K., Jain, A., Choi, J. M., Saltzman, A., Christenson, A., Jung, S. Y., Malovannaya, A., Grimson, A.. 2018-11-20. MiR-146a wild-type 3’ sequence identity is dispensable for proper innate immune function in vivo. https://doi.org/10.1101/474791

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