From a retrovirus infection of mice to a long noncoding RNA that induces proto-oncogene transcription and oncogenesis via an epigenetic transcription switch

从小鼠逆转录病毒感染到通过表观遗传转录开关诱导原癌基因转录和肿瘤发生的长链非编码RNA

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Abstract

Here I review the properties of the mouse retroelement VL30-1, which apparently derived from retrotranspostions of a founder VL30 retrovirus that infected the mouse germline after the mouse-human speciation. The VL30-1 gene is transcribed as a long noncoding RNA (lncRNA) with an essential host function in an epigenetic transcription switch (ETS) that regulates transcription of multiple genes, including proto-oncogenes that control cell proliferation and oncogenesis. The ETS involves the tumor suppressor protein PSF that has a DNA-binding domain (DBD) and two RNA-binding domains (RBDs). The DBD binds to promoters that have a DBD-binding sequence and switches off transcription, and the RBDs bind lncRNAs that have a RBD-binding sequence, releasing PSF and switching on transcription. VL30-1 lncRNA has two RBD-binding sequences, apparently acquired by mutations during retrotranspositions of the founder retrovirus, which drive proto-oncogene transcription and oncogenesis via the ETS. VL30-1 lncRNA is a seminal example of the key role of endogenous retroviruses (ERVs) and their retroelements in the evolution of transcription regulatory systems.

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