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 PMID:30777858  

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

Grant Bertolet | Natee Kongchan | Rebekah Miller | Ravi K Patel | Antrix Jain | Jong Min Choi | Alexander B Saltzman | Amber Christenson | Sung Yun Jung | Anna Malovannaya | Andrew Grimson | Joel R Neilson
Life science alliance | 2019

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.

Pubmed ID: 30777858

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA190467
  • Agency: NCI NIH HHS, United States
    Id: P30 CA125123
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI053831
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI036211
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR024574
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK060445
  • Agency: NICHD NIH HHS, United States
    Id: P50 HD076210

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