Mantziou Stefania, Markopoulos Georgios S
Haematology Laboratory-Unit of Molecular Biology, University Hospital of Ioannina, 45110 Ioannina, Greece.
Neurosurgical Institute, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece.
Biomedicines. 2021 Nov 22;9(11):1742. doi: 10.3390/biomedicines9111742.
Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles (SEVs) through an SEV enrichment sequence. We analysed VL30 elements for the presence of the distinct 26 nt SEV enrichment motif and found that SEV enrichment is an inherent hallmark of the VL30 family, contained in 36 full-length elements, with a widespread chromosomal distribution. Among them, 25 elements represent active, present-day integrations and contain an abundance of regulatory sequences. Phylogenetic analysis revealed a recent spread of SEV-VL30s from 4.4 million years ago till today. Importantly, 39 elements contain an SFPQ-binding motif, associated with the transcriptional induction of oncogenes. Most SEV-VL30s reside in transcriptionally active regions, as characterised by their distribution adjacent to candidate cis-regulatory elements (cCREs). Network analysis of SEV-VL30-associated genes suggests a distinct transcriptional footprint associated with embryonal abnormalities and neoplasia. Given the established role of VL30s in oncogenesis, we conclude that their potential to spread through SEVs represents a novel mechanism for non-coding RNA biology with numerous implications for cellular homeostasis and disease.
长链非编码RNA（lncRNAs）在基因组时代之后已成为重要的表观遗传调控因子。病毒样30元件（VL30s）是一类小鼠逆转录转座子家族，可转录为功能性lncRNAs。最近的数据表明，VL30 RNAs通过一个细胞外小泡（SEV）富集序列有效地包装在细胞外小泡中。我们分析了VL30元件中独特的26个核苷酸的SEV富集基序的存在情况，发现SEV富集是VL30家族的一个固有特征，存在于36个全长元件中，具有广泛的染色体分布。其中，25个元件代表活跃的、现今的整合，并且包含大量的调控序列。系统发育分析显示，SEV-VL30s从440万年前至今有一个近期的传播过程。重要的是，39个元件包含一个与癌基因转录诱导相关的SFPQ结合基序。大多数SEV-VL30s位于转录活跃区域，其特征是它们分布在候选顺式调控元件（cCREs）附近。对SEV-VL30相关基因的网络分析表明，存在一个与胚胎异常和肿瘤形成相关的独特转录足迹。鉴于VL30s在肿瘤发生中的既定作用，我们得出结论，它们通过SEVs传播的潜力代表了一种非编码RNA生物学的新机制，对细胞稳态和疾病有诸多影响。
