A retroviral origin of vertebrate myelin
A retroviral origin of vertebrate myelin
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DOI：
10.1101/2022.01.24.477350
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发表时间：
2022-01
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通讯作者：
Tanay Ghosh;R. Almeida;Chao Zhao;A. Mannioui;E. Martin;Alex Fleet;Ginez Gonzalez M;D. Rowitch;K. Stott;I. Adams;B. Zalc;N. Goldman;D. Lyons;R. Franklin
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作者：
Tanay Ghosh;R. Almeida;Chao Zhao;A. Mannioui;E. Martin;Alex Fleet;Ginez Gonzalez M;D. Rowitch;K. Stott;I. Adams;B. Zalc;N. Goldman;D. Lyons;R. Franklin
髓鞘是由中枢神经系统（CNS）中的少突胶质细胞产生的包围神经元轴突的绝缘鞘。这种进化创新首先出现在有颌脊椎动物中，使神经冲动的快速传递、更复杂的大脑和更大的形态多样性成为可能。在这里，我们报告RNLTR 12-int，逆转录病毒来源的逆转录转座子，RNA水平的表达是髓鞘形成所必需的。我们发现RNLTR 12-int编码的非编码RNA与转录因子SOX 10结合，调节啮齿动物髓鞘碱性蛋白（Mbp，髓鞘的主要成分）的转录。RNLTR 12-int样序列（我们称之为RetroMyelin）在所有有颌脊椎动物中发现，我们进一步证明了它们在两种不同脊椎动物门（斑马鱼和青蛙）中调节髓鞘形成的功能。因此，我们的研究表明，逆转录病毒内源化是脊椎动物髓鞘出现的关键步骤。
Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains and greater morphological diversity. Here we report that RNA level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show RNLTR12-int-encoded non-coding RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int like sequences (which we name RetroMyelin) are found in all jawed-vertebrates and we further demonstrate their function in regulating myelination in two different vertebrate phyla (zebrafish and frogs). Our study therefore suggests that retroviral endogenization was a key step in the emergence of vertebrate myelin.