通过反义长非编码 RNA 对 Egr2 的转录缓冲来调节外周髓鞘形成。
Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA.
机构信息
Molecular Neuroscience and Neuro-Oncology Laboratory, Geisinger Clinic, Danville, PA 17822, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Cell Rep. 2017 Aug 22;20(8):1950-1963. doi: 10.1016/j.celrep.2017.07.068.
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.
精确调控 Egr2 转录对于控制周围髓鞘形成至关重要。在这里，我们描述了一种与 Egr2 启动子反义的长非编码 RNA（Egr2-AS-RNA）。在周围神经损伤时，Egr2-AS-RNA 的表达增加，与 Egr2 转录本和蛋白水平降低相关。Egr2-AS-RNA 在背根神经节（DRG）培养物中的异位表达抑制 Egr2 mRNA 的表达并诱导脱髓鞘。坐骨神经损伤后，从可生物降解水凝胶中释放的寡核苷酸 GapMers 抑制 Egr2-AS-RNA 的表达，可逆转 EGR2 介导的基因表达谱，并显著延迟脱髓鞘。Egr2-AS-RNA 在坐骨神经损伤后逐渐募集 Egr2 启动子上的 H3K27ME3、AGO1、AGO2 和 EZH2。此外，Egr2-AS-RNA 的表达通过 ERK1/2 信号通路调控 YY1，而 YY1 的 Ser184 缺失调节与 Egr2-AS-RNA 的结合。总之，我们描述了对周围神经系统（PNS）生物学中反义长非编码 RNA 的功能探索。
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