PT  - JOURNAL ARTICLE
AU  - Bertolet, Grant
AU  - Kongchan, Natee
AU  - Miller, Rebekah
AU  - Patel, Ravi K
AU  - Jain, Antrix
AU  - Choi, Jong Min
AU  - Saltzman, Alexander B
AU  - Christenson, Amber
AU  - Jung, Sung Yun
AU  - Malovannaya, Anna
AU  - Grimson, Andrew
AU  - Neilson, Joel R
TI  - MiR-146a wild-type 3′ sequence identity is dispensable for proper innate immune function in vivo
AID  - 10.26508/lsa.201800249
DP  - 2019 Feb 01
TA  - Life Science Alliance
PG  - e201800249
VI  - 2
IP  - 1
4099  - http://www.life-science-alliance.org/content/2/1/e201800249.short
4100  - http://www.life-science-alliance.org/content/2/1/e201800249.full
SO  - Life Sci. Alliance2019 Feb 01; 2
AB  - 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 Caenorhabditis 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'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 mir-146a–null mice. Our results indicate that 3′ pairing is dispensable for the established myeloid function of this key mammalian microRNA.