Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis.

ABSTRACT: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3' UTR of Irak-1 gene via Ago2 binding. miR-146a knockout in mice offers protection against sepsis with attenuated interleukin-6 (IL-6) storm and o

SUBMITTER: Wang S 

PROVIDER: S-EPMC8633977 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature