Pseudogenes regulate parental gene expression via ceRNA network

Abstract

The concept of competitive endogenous RNA (ceRNA) was first proposed by Salmena and colleagues. Evidence suggests that pseudogene RNAs can act as a ‘sponge’ through competitive binding of common miRNA, releasing or attenuating repression through sequestering miRNAs away from parental mRNA. In theory, ceRNAs refer to all transcripts such as mRNA, tRNA, rRNA, long non‐coding RNA, pseudogene RNA and circular RNA, because all of them may become the targets of miRNA depending on spatiotemporal situation. As binding of miRNA to the target RNA is not 100% complementary, it is possible that one miRNA can bind to multiple target RNAs and vice versa. All RNAs crosstalk through competitively binding to miRNA via miRNA response elements (MREs) contained within the RNA sequences, thus forming a complex regulatory network. The ratio of a subset of miRNAs to the corresponding number of MREs determines repression strength on a given mRNA translation or stability. An increase in pseudogene RNA level can sequester miRNA and release repression on the parental gene, leading to an increase in parental gene expression. A massive number of transcripts constitute a complicated network that regulates each other through this proposed mechanism, though some regulatory significance may be mild or even undetectable. It is possible that the regulation of gene and pseudogene expression occurring in this manor involves all RNAs bearing common MREs. In this review, we will primarily discuss how pseudogene transcripts regulate expression of parental genes via ceRNA network and biological significance of regulation.

Long non‐coding RNA TCONS_00041960 enhances osteogenesis and inhibits adipogenesis of rat bone marrow mesenchymal stem cell by targeting miR‐204‐5p and miR‐125a‐3p

“…Through luciferase reporter assays, we confirmed that TCONS_00041960 recognized the seed regions of miR‐204‐5p and miR‐125a‐3p. Furthermore, RIP and SPR assays showed that TCONS_00041960 functioned as a sponge of miR‐204‐5p and miR‐125a‐3p, and thus sequesters them from potential mRNAs (An, Furber, & Ji, ). We also found that siRNA against TCONS_00041960 increased miR‐204‐5p and miR‐125a‐3p expression.…”

Transcriptional and Post-Transcriptional Gene Regulation by Long Non-Coding RNA

“…Clearly, a non-coding transcript that shares a high degree of homology with a coding gene is likely to share many of its MREs and therefore pseudogenes are good candidates to act as ceRNAs. Indeed, this seems to be the case [13], [47], [48]. Examples of such lncRNAs include a pseudogene homologous to the gene encoding tumour suppressor phosphatase and tensin homologue ( PTEN ), which contains multiple MREs within the 3′UTR shared with the coding gene [48], as well as pseudogenes homologous to the 3′UTRs of the genes encoding tumour suppressor candidate 2 ( TUSC2 ) [49] and forkhead box protein O1 ( FOXO1 ) [50].…”

Current best practices in single‐cell RNA‐seq analysis: a tutorial

“…To reduce the multiple testing burden, transcripts that may not be of interest can be excluded from the dataset. While pseudogenes or non‐coding RNAs can be informative (An et al , ), they are often ignored in the analysis.…”