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2017 ; 8
(ä): 583
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An Expanded Role for HLA Genes: HLA-B Encodes a microRNA that Regulates IgA and
Other Immune Response Transcripts
#MMPMID28579988
Chitnis N
; Clark PM
; Kamoun M
; Stolle C
; Brad Johnson F
; Monos DS
Front Immunol
2017[]; 8
(ä): 583
PMID28579988
show ga
We describe a novel functional role for the HLA-B locus mediated by its
intron-encoded microRNA (miRNA), miR-6891-5p. We show that in vitro inhibition of
miR-6891-5p impacts the expression of nearly 200 transcripts within the
B-lymphoblastoid cell line (B-LCL) COX, affecting a large number of metabolic
pathways, including various immune response networks. The top affected
transcripts following miR-6891-5p inhibition are those encoding the heavy chain
of IgA. We identified a conserved miR-6891-5p target site on the 3'UTR of both
immunoglobulin heavy chain alpha 1 and 2 (IGHA1 and IGHA2) transcripts and
demonstrated that this miRNA modulates the expression of IGHA1 and IGHA2. B-LCLs
from IgA-deficient patients expressed significantly elevated levels of
miR-6891-5p when compared with unaffected family members. Upon inhibition of
miR-6891-5p, IgA mRNA expression levels were increased, and IgA secretion was
restored in the B-LCL of an IgA-deficient patient. These findings indicate that
miR-6891-5p regulates IGHA1 and IGHA2 gene expression at the posttranscriptional
level and suggest that increase in miR-6891-5p levels may contribute to the
etiology of selective IgA deficiency.