University of the Basque Country, UPV-EHU, Leioa, Spain.
Biobizkaia Health Research Institute, Barakaldo, Spain.
Commun Biol. 2023 Sep 5;6(1):908. doi: 10.1038/s42003-023-05278-z.
Long noncoding RNAs have been identified in most vertebrates, but the functional characterization of these molecules is challenging, mainly due to the lack of linear sequence homology between species. In this work, we aimed to find functional evolutionary convergent lncRNAs involved in development by screening of k-mer content (nonlinear similarity) and secondary structure-based approaches combining in silico, in vitro and in vivo validation analysis. From the Madagascar gecko genes, we have found a non-orthologous lncRNA with a similar k-mer content and structurally concordant with the human lncRNA EVX1AS. Analysis of function-related characteristics together with locus-specific targeting of human EVX1AS and gecko EVX1AS-like (i.e., CRISPR Display) in human neuroepithelial cells and chicken mesencephalon have confirmed that gecko EVX1AS-like lncRNA mimics human EVX1AS function and induces EVX1 expression independently of the target species. Our data shows functional convergence of non-homologous lncRNAs and presents a useful approach for the definition and manipulation of lncRNA function within different model organisms.
长非编码 RNA 已在大多数脊椎动物中被鉴定出来，但这些分子的功能特征分析具有挑战性，主要是由于物种之间缺乏线性序列同源性。在这项工作中，我们旨在通过筛选 k- -mer 含量（非线性相似性）和基于二级结构的方法，结合计算机模拟、体外和体内验证分析，寻找与发育相关的功能进化上趋同的 lncRNA。从马达加斯加壁虎基因中，我们发现了一个非同源的 lncRNA，其 k- -mer 含量相似，与人类 lncRNA EVX1AS 的结构一致。对功能相关特征的分析，以及对人类神经上皮细胞和鸡中脑的人类 EVX1AS 和壁虎 EVX1AS 样（即 CRISPR 显示）的特定基因座靶向分析，证实了壁虎 EVX1AS 样 lncRNA 模拟了人类 EVX1AS 的功能，并独立于靶物种诱导 EVX1 的表达。我们的数据表明了非同源 lncRNA 的功能趋同，并为在不同的模式生物中定义和操纵 lncRNA 功能提供了一种有用的方法。
