Circular RNA of the human sphingomyelin synthase 1 gene: Multiple splice variants, evolutionary conservatism and expression in different tissues

Abstract

The human sphingomyelin synthase 1 gene (SGMS1) encodes an essential enzyme that is involved in the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide. Among the products of SGMS1, we found new transcripts, circular RNAs (circRNAs), that contain sequences of the gene's 5 0 untranslated region (5 0 UTR). Some of them include the gene's coding region and fragments of introns. An analysis of the abundance of circRNAs in human tissues showed that the largest transcripts were predominantly found in different parts of the brain. circRNAs of rat and mouse sphingomyelin synthase 1 orthologous genes were detected and are highly similar to the human SGMS1 gene transcripts. A quantitative analysis of the abundance of such transcripts also revealed their elevated amount in the brain. A computational analysis of sequences of human circRNAs showed their high potential of binding microRNAs (miRNAs), including the miRNAs that form complexes with Ago proteins and the mRNA of SGMS1. We assume that the circRNAs identified here participate in the regulation of the function of the SGMS1 gene in the brain.

The Role of Noncoding RNAs in Brain Cells during Rat Cerebral Ischemia

“…To date, there is evidence that a substantial part of long ncRNA exists in a circular form [49][50][51][52][53][54]. Circular RNA (circRNA) is a newly discovered and relatively poorly studied class of long ncRNA, found predominantly in mammalian cells.…”

“…ceramide [59][60][61][62][63]. In addition to mRNAs providing protein synthesis, 13 circRNAs that predominantly contained sequences of the multi-exon 5′-untranslated region of the gene (5′-UTR) have been identified [54]. The RS-exons that participate in the multistep splicing of long introns of the gene were found within six circRNAs of the SGMS1 gene.…”

“…So, homologous exons of these genes are detected in circRNA [64]. Most human and rodent circRNAs have predominantly brain-specific expression [54,[65][66][67][68]. In particular, it has been shown that circRNAs are predominantly localized in areas of neurons (axons and dendrites).…”

Circular RNAs: Isolation, characterization and their potential role in diseases

“… 52 Filippenkov et al. also showed that circRNAs containing sequences of the gene's 5′ untranslated region (5′UTR) of the human sphingomyelin synthase 1 gene ( SGMS1 ) were found predominantly in different parts of the brain, and regulated the function of the SGMS1 gene in the brain, 53 while the SGNS1 gene encodes a transmembrane protein participating in sphingomyelin synthesis, intracellular molecular transport regulation, cholesterol metabolism, cell proliferation, and apoptosis. 54-56 CircRNAs are very abundant in the mammalian brain, as well as through neuronal differentiation, especially in synapses, and with their high stability, neuronal termini might use them and they might perform as synaptic tags to maintain a molecular memory.…”

Comprehensive Assessment of Sequence and Expression of Circular-RNAs in Progenitor Cell Types of the Developing Mammalian Cortex

“…Despite their abundance, predicting circRNAs remains burdensome and typically relies on bioinformatic tools identifying sequences across backsplice junctions from RNA sequencing data obtained upon depletion of ribosomal RNA 15 . Although this has resulted in the prediction of thousands of potential circRNAs in cell lines or whole organs of many species 6,11,13,[16][17][18][19] , this approach based on ribosomal RNA depletion has the critical limitation that reads that do not map on a backsplice junction cannot be assigned to a circular, as opposed to a linear, transcript resulting in the exclusion of the overwhelming majority of the sequencing data. In turn, this makes it impossible to reliably reconstruct neither the full sequence nor the expression level of large pools of circRNAs.…”