BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA.
Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado 80302, USA.
RNA. 2022 Jun;28(6):842-853. doi: 10.1261/rna.079070.121. Epub 2022 Mar 18.
Long noncoding RNAs (lncRNAs) are rapidly evolving and thus typically poorly conserved in their sequences. How these sequence differences affect the characteristics and potential functions of lncRNAs with shared synteny remains unclear. Here we show that the syntenically conserved lncRNA displays distinct expression and localization patterns in human and mouse. Single molecule RNA FISH reveals that in a range of cell lines, mouse () is predominantly nuclear, while human () is distributed between the cytoplasm and nucleus. This localization pattern is maintained in human/mouse hybrid cells expressing both human and mouse , implying that the localization of the lncRNA is species autonomous. We find that the majority of transcripts in the cytoplasm are comprised of isoforms that are enriched in RRD repeats. We furthermore determine that in various tissues, is more highly expressed than its human counterpart. Our data illustrate that the rapid evolution of syntenic lncRNAs can lead to variations in lncRNA localization and abundance, which in turn may result in disparate lncRNA functions even in closely related species.
长非编码 RNA(lncRNA)在进化过程中迅速变化,因此其序列通常在种间保守性较差。这些序列差异如何影响具有共线性的 lncRNA 的特征和潜在功能尚不清楚。在这里,我们展示了共线性保守的 lncRNA 在人和小鼠中表现出不同的表达和定位模式。单分子 RNA FISH 揭示,在一系列细胞系中,小鼠的 () 主要位于核内,而人类的 () 则分布在细胞质和核内。这种定位模式在表达人和小鼠的杂种细胞中得以维持,这意味着 lncRNA 的定位是物种自主的。我们发现,细胞质中大多数的 () 转录本包含富含 RRD 重复的亚型。此外,我们还确定在不同的组织中,() 的表达水平高于其人类对应物。我们的数据表明,共线性 lncRNA 的快速进化会导致 lncRNA 定位和丰度的变化,这反过来可能导致即使在密切相关的物种中,lncRNA 功能也存在差异。