Down regulated IncRNA MEG3 eliminates mycobacteria in macrophages via autophagy

作者：Pawar Kamlesh; Hanisch Carlos; Vera Sergio Eliseo Palma; Einspanier Ralf; Sharbati Soroush^*

来源：Scientific Reports, 2016, 6(1): 19416.

DOI：10.1038/srep19416

Small non-coding RNA play a major part in host response to bacterial agents. However, the role of long non-coding RNA (IncRNA) in this context remains unknown. LncRNA regulate gene expression by acting e.g. as transcriptional coactivators, RNA decoys or microRNA sponges. They control development, differentiation and cellular processes such as autophagy in disease conditions. Here, we provide an insight into the role of IncRNA in mycobacterial infections. Human macrophages were infected with Mycobacterium bovis BCG and IncRNA expression was studied early post infection. For this purpose, IncRNA with known immune related functions were preselected and a IncRNA specific RT-qPCR protocol was established. In addition to expression-based prediction of IncRNA function, we assessed strategies for thorough normalisation of IncRNA. Arrayed quantification showed infection dependent repression of several IncRNA including MEG3. Pathway analysis linked MEG3 to mTOR and PI3K-AKT signalling pointing to regulation of autophagy. Accordingly, IFN-gamma induced autophagy in infected macrophages resulted in sustained MEG3 down regulation and lack of IFN-gamma allowed for counter regulation of MEG3 by viable M. bovis BCG. Knockdown of MEG3 in macrophages resulted in induction of autophagy and enhanced eradication of intracellular M. bovis BCG.

• 出版日期2016-1-13