Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA

Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Margot Martinez-Moreno, Timothy Mark O'Shea, John P. Zepecki, Alexander Olaru, Jennifer K. Ness, Robert Langer, Nikos Tapinos
Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA). During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG) cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS) biology.

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Teaser

Martinez-Moreno et al. report a role for a long non-coding RNA antisense to the promoter of Egr2, Egr2-AS-RNA, during the response to peripheral nerve injury. Inhibition of Egr2-AS-RNA following sciatic nerve injury reverts EGR2-mediated gene expression and delays demyelination.


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