Scarola Michele, Comisso Elisa, Rosso Massimo, Del Sal Giannino, Schneider Claudio, Schoeftner Stefan, Benetti Roberta
Laboratorio Nazionale-Consorzio Interuniversitario per le Biotecnologie, Laboratorio Nazionale (LNCIB), Padriciano 99, 34149, Trieste, Italy.
Dipartimento di Area Medica (DAME), Università degli Studi di Udine, p.le Kolbe 4, 33100, Udine, Italy.
Commun Biol. 2020 Oct 30;3(1):632. doi: 10.1038/s42003-020-01355-9.
The resurrection of pseudogenes during evolution produced lncRNAs with new biological function. Here we show that pseudogene-evolution created an Oct4 pseudogene lncRNA that is able to direct epigenetic silencing of the parental Oct4 gene via a 2-step, lncRNA dependent mechanism. The murine Oct4 pseudogene 4 (mOct4P4) lncRNA recruits the RNA binding protein FUS to allow the binding of the SUV39H1 HMTase to a defined mOct4P4 lncRNA sequence element. The mOct4P4-FUS-SUV39H1 silencing complex holds target site specificity for the parental Oct4 promoter and interference with individual components results in loss of Oct4 silencing. SUV39H1 and FUS do not bind parental Oct4 mRNA, confirming the acquisition of a new biological function by the mOct4P4 lncRNA. Importantly, all features of mOct4P4 function are recapitulated by the human hOCT4P3 pseudogene lncRNA, indicating evolutionary conservation. Our data highlight the biological relevance of rapidly evolving lncRNAs that infiltrate into central epigenetic regulatory circuits in vertebrate cells.
在进化过程中假基因的复活产生了具有新生物学功能的长链非编码RNA（lncRNA）。在此我们表明，假基因进化产生了一种Oct4假基因lncRNA，它能够通过一种两步的、依赖lncRNA的机制指导亲代Oct4基因的表观遗传沉默。小鼠Oct4假基因4（mOct4P4）lncRNA招募RNA结合蛋白FUS，以使SUV39H1组蛋白甲基转移酶（HMTase）结合到特定的mOct4P4 lncRNA序列元件上。mOct4P4 - FUS - SUV39H1沉默复合物对亲代Oct4启动子具有靶位点特异性，干扰单个组分会导致Oct4沉默丧失。SUV39H1和FUS不与亲代Oct4 mRNA结合，证实了mOct4P4 lncRNA获得了新的生物学功能。重要的是，人hOCT4P3假基因lncRNA概括了mOct4P4功能的所有特征，表明其具有进化保守性。我们的数据突出了快速进化的lncRNAs在脊椎动物细胞中渗透到核心表观遗传调控回路的生物学相关性。
