AUTHOR=Zhou Hongjian , Wu Shanshan , Liu Li , Li Ruimin , Jin Ping , Li Shengjie 

TITLE=Drosophila Relish Activating lncRNA-CR33942 Transcription Facilitates Antimicrobial Peptide Expression in Imd Innate Immune Response

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.905899

DOI=10.3389/fimmu.2022.905899

ISSN=1664-3224

ABSTRACT=<p>Long noncoding RNAs (lncRNAs) are an emerging class of regulators that play crucial roles in regulating the strength and duration of innate immunity. However, little is known about the regulation of <italic>Drosophila</italic> innate immunity-related lncRNAs. In this study, we first revealed that overexpression of <italic>lncRNA-CR33942</italic> could strengthen the expression of the Imd pathway antimicrobial peptide (AMP) genes <italic>Diptericin</italic> (<italic>Dpt</italic>) and <italic>Attacin-A</italic> (<italic>AttA</italic>) after infection, and vice versa. Secondly, RNA-seq analysis of <italic>lncRNA-CR33942</italic>-overexpressing flies post Gram-negative bacteria infection confirmed that <italic>lncRNA-CR33942</italic> positively regulated the <italic>Drosophila</italic> immune deficiency (Imd) pathway. Mechanistically, we found that <italic>lncRNA-CR33942</italic> interacts and enhances the binding of NF-κB transcription factor Relish to <italic>Dpt</italic> and <italic>AttA</italic> promoters, thereby facilitating <italic>Dpt</italic> and <italic>AttA</italic> expression. Relish could also directly promote <italic>lncRNA-CR33942</italic> transcription by binding to its promoter. Finally, rescue experiments and dynamic expression profiling post-infection demonstrated the vital role of the Relish/<italic>lncRNA-CR33942</italic>/AMP regulatory axis in enhancing Imd pathway and maintaining immune homeostasis. Our study elucidates novel mechanistic insights into the role of <italic>lncRNA-CR33942</italic> in activating <italic>Drosophila</italic> Imd pathway and the complex regulatory interaction during the innate immune response of animals.</p>