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

ABSTRACT: A long-prevailing model has held that the “seed” region (nucleotides 2-8) of a microRNA is typically sufficient to mediate target recognition and repression. However, numerous recent studies, both within the context of defining miRNA/target pairs by direct physical association and by directly assessing this model in vivo in C. elegans have brought this model into question. To test the importance of miRNA 3' pairing in vivo, in a mammalian system, we engineered a mutant murine mir-146a allele in which the 5' half of the mature microRNA retains the sequence of the wild-type mir-146a but the 3ʹ half has been altered to be anti-complementary to the wild-type miR-146a sequence. 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 strongly support the conclusion that 3ʹ pairing is dispensable in the context of the function of a key mammalian microRNA.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Enterococcus Faecalis (streptococcus Faecalis) Heliocidaris Erythrogramma (sea Urchin) Acyrthosiphon Pisum (pea Aphid) Bombyx Mori (silk Moth) Pan Troglodytes (chimpanzee) Candida Albicans (yeast) Pinus Radiata (monterey Pine) Brassica Oleracea Var. Botrytis (cauliflower) Helicobacter Pylori J99 (campylobacter Pylori J99) Saccharomyces Cerevisiae (baker's Yeast) Merluccius Bilinearis (silver Hake) Halobacterium Salinarum Drosophila Melanogaster (fruit Fly) Hepatitis C Virus Subtype 1a Pongo Pygmaeus (bornean Orangutan) Escherichia Coli Ictalurus Punctatus (channel Catfish) Hordeum Vulgare (barley) Brassica Napus (rape) Staphylococcus Aureus Ricinus Communis Arabidopsis Thaliana (mouse-ear Cress) Dictyostelium Discoideum (slime Mold) Olea Europaea (common Olive) Gadus Morhua (atlantic Cod) Rattus Norvegicus (rat) Equus Caballus (horse) Pisum Sativum (garden Pea) Caenorhabditis Elegans Danio Rerio (zebrafish) (brachydanio Rerio) Solanum Tuberosum (potato) Oryza Sativa (rice) Rattus Rattus (black Rat) Macaca Mulatta (rhesus Macaque) Arachis Hypogaea (peanut) Mesocricetus Auratus (golden Hamster) Nicotiana Tabacum (common Tobacco) Cercopithecus Aethiops (green Monkey) (grivet) Homo Sapiens (human) Bos Taurus (bovine) Gallus Gallus (chicken) Cicer Arietinum (chickpea) (garbanzo) Apis Mellifera (honeybee) Mus Musculus (mouse)

TISSUE(S): Primary Cell, Stem Cell

SUBMITTER: Bhoomi Bhatt  

LAB HEAD: Joel Neilson

PROVIDER: PXD011413 | Pride | 2019-02-09

REPOSITORIES: Pride