@article {Bertolete201800249, author = {Grant Bertolet and Natee Kongchan and Rebekah Miller and Ravi K Patel and Antrix Jain and Jong Min Choi and Alexander B Saltzman and Amber Christenson and Sung Yun Jung and Anna Malovannaya and Andrew Grimson and Joel R Neilson}, title = {MiR-146a wild-type 3' sequence identity is dispensable for proper innate immune function in vivo}, volume = {2}, number = {1}, elocation-id = {e201800249}, year = {2019}, doi = {10.26508/lsa.201800249}, publisher = {Life Science Alliance}, abstract = {The prevailing model of microRNA function is that the {\textquotedblleft}seed region{\textquotedblright} (nt 2{\textendash}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{\textendash}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{\textquoteright}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{\textendash}null mice. Our results indicate that 3' pairing is dispensable for the established myeloid function of this key mammalian microRNA.}, URL = {https://www.life-science-alliance.org/content/2/1/e201800249}, eprint = {https://www.life-science-alliance.org/content/2/1/e201800249.full.pdf}, journal = {Life Science Alliance} }