NF-κB factors cooperate with Su(Hw)/E4F1 to balance Drosophila/human immune responses via modulating dynamic expression of miR-210.
Nucleic Acids Res
; 52(12): 6906-6927, 2024 Jul 08.
Article
in En
| MEDLINE
| ID: mdl-38742642
ABSTRACT
MicroRNAs (miRNAs) play crucial regulatory roles in controlling immune responses, but their dynamic expression mechanisms are poorly understood. Here, we firstly confirm that the conserved miRNA miR-210 negatively regulates innate immune responses of Drosophila and human via targeting Toll and TLR6, respectively. Secondly, our findings demonstrate that the expression of miR-210 is dynamically regulated by NF-κB factor Dorsal in immune response of Drosophila Toll pathway. Thirdly, we find that Dorsal-mediated transcriptional inhibition of miR-210 is dependent on the transcriptional repressor Su(Hw). Mechanistically, Dorsal interacts with Su(Hw) to modulate cooperatively the dynamic expression of miR-210 in a time- and dose-dependent manner, thereby controlling the strength of Drosophila Toll immune response and maintaining immune homeostasis. Fourthly, we reveal a similar mechanism in human cells, where NF-κB/RelA cooperates with E4F1 to regulate the dynamic expression of hsa-miR-210 in the TLR immune response. Overall, our study reveals a conservative regulatory mechanism that maintains animal innate immune homeostasis and provides new insights into the dynamic regulation of miRNA expression in immune response.
Full text:
1
Database:
MEDLINE
Main subject:
Transcription Factors
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Drosophila Proteins
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MicroRNAs
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Immunity, Innate
Limits:
Animals
/
Humans
Language:
En
Year:
2024
Type:
Article