Molecular Evolution of the Non-Coding Eosinophil Granule Ontogeny Transcript

Abstract

Eukaryotic genomes are pervasively transcribed. A large fraction of the transcriptional output consists of long, mRNA-like, non-protein-coding transcripts (mlncRNAs). The evolutionary history of mlncRNAs is still largely uncharted territory. In this contribution, we explore in detail the evolutionary traces of the eosinophil granule ontogeny transcript (EGOT), an experimentally confirmed representative of an abundant class of totally intronic non-coding transcripts (TINs). EGOT is located antisense to an intron of the ITPR1 gene. We computationally identify putative EGOT orthologs in the genomes of 32 different amniotes, including orthologs from primates, rodents, ungulates, carnivores, afrotherians, and xenarthrans, as well as putative candidates from basal amniotes, such as opossum or platypus. We investigate the EGOT gene phylogeny, analyze patterns of sequence conservation, and the evolutionary conservation of the EGOT gene structure. We show that EGO-B, the spliced isoform, may be present throughout the placental mammals, but most likely dates back even further. We demonstrate here for the first time that the whole EGOT locus is highly structured, containing several evolutionary conserved, and thermodynamic stable secondary structures. Our analyses allow us to postulate novel functional roles of a hitherto poorly understood region at the intron of EGO-B which is highly conserved at the sequence level. The region contains a novel ITPR1 exon and also conserved RNA secondary structures together with a conserved TATA-like element, which putatively acts as a promoter of an independent regulatory element.

Identifying Novel Glioma-Associated Noncoding RNAs by Their Expression Profiles

“…It is worth mentioning that secondary GBMs are relatively rare, partly because precursor low-grade or anaplastic astrocytoma develop at younger age than other GBMs, and some patients succumb before the disease progresses, and partly because they are mistakenly classified as primary GBMs [ 72 ]. EGO-A function is not yet known [ 73 ], but its potential role in glioma biogenesis may be implied by the chromosomal location, since its host gene ITPR1 (inositol triphosphate receptor type 1) is encoded in close proximity to EGR-1 (early growth response 1), a transcriptional regulator of genes required for induction of mitosis, cell differentiation, and growth [ 74 ]. Expression of EGR-1 gene in glioma cells is induced by overexpression of EGFR and PDGFR genes, thus suggesting EGR-1 as a connection of growth factor stimulation with gene expression changes [ 74 ].…”

EGOT lncRNA in head and neck squamous cell carcinomas

“…It has two known isoforms -EGO-A (unspliced) and EGO-B (spliced) -that share the same transcriptional start site and both are polyadenylated. EGOT regulates eosinophil granule protein expression during eosinophil cells developmental process and functions as a non-coding RNA [9,10]. Numerous recent studies have been dedicated to understanding the role of EGOT in glioma [11], breast cancer [12], gastric cancer [13], haematological malignancies [14] and in viral infections [15,16,17] and in cardiology [18,19].…”

Long noncoding RNA eosinophil granule ontogeny transcript inhibits cell proliferation and migration and promotes cell apoptosis in human glioma

“…Among the functional lncRNAs, the majority have been implicated in malignant tumors (10,21). The lncRNA, EGOT, was initially thought to be involved in eosinophil development and expressed in mature eosinophils (16); it was subsequently demonstrated that EGOT locus is highly structured, containing several evolutionary conserved regions, and thermodynamic stable secondary structures (22). Notably, the functional roles of EGOT have recently been implicated in ischemic heart diseases (23).…”