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

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.

Related Concepts

Alleles
Enzyme Repression
Laboratory mice
Nucleotides
Physiological Aspects
RNA, Messenger
Caenorhabditis elegans
Recognition (Psychology)
Mutant
MicroRNAs

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