Noncoding RNAs: Master Regulators of Inflammatory Signaling Chew, Chen Li et al. Trends in Molecular Medicine, Volume 24, Issue 1, 66 - 84
Abstract:
ncRNAs have been shown to interact with proteins to influence downstream signaling events. For instance, NKILA has been shown to bind to the nuclear factor-κB (NF-κB)/IκB complex, which masks the phosphorylation sites of IκB, thus preventing its degradation.
Long ncRNAs (lncRNAs) have been found to interact with heterogeneous nuclear ribonucleoproteins (hnRNPs) to modulate transcription. lincRNA-EPS and THRIL can interact with hnRNPL
Genetic mouse knockout models of lncRNAs can provide further evidence of their physiological relevance. lincRNA-EPS knockout has resulted in enhanced inflammatory responses, supporting its role in repressing the expression of immune response genes
Unbiased approaches, using RNA-seq, microarray, or CRISPR-Cas9 screens, have helped identify ncRNAs important in inflammation, such as THRIL, lincRNA-Cox2, and lincRNA-EPS.
New avenues of therapeutic intervention might be provided by targeting ncRNAs with cellular specificity, offering the possibility of the subtle manipulation of inflammatory signaling pathways relevant to various pathologies.
Inflammatory signaling underlies many diseases, from arthritis to cancer. Our understanding of inflammation has thus far been limited to the world of proteins, because we are only just beginning to understand the role that noncoding RNAs (ncRNA) might play. It is now clear that ncRNA do not constitute transcriptional ‘noise’ but instead harbor physiological functions in controlling signaling pathways. In this review, we cover the newly discovered mechanisms and functions of ncRNAs in the regulation of inflammatory signaling. We also describe advances in experimental techniques allowing this field of research to take root. These findings have opened new avenues for putative therapeutic intervention in inflammatory diseases, which may be seen translated into clinical outcomes in the future.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research is supported by core funding from Institute of Molecular and Cell Biology.