Pseudogenes regulate parental gene expression via ceRNA network

Abstract

The concept of competitive endogenous RNA (ce RNA) was first proposed by Salmena and colleagues. Evidence suggests that pseudogene RNAs can act as a ‘sponge’ through competitive binding of common mi RNA, releasing or attenuating repression through sequestering mi RNAs away from parental mRNA. In theory, ce RNAs 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 mi RNA depending on spatiotemporal situation. As binding of mi RNA to the target RNA is not 100% complementary, it is possible that one mi RNA can bind to multiple target RNAs and vice versa. All RNAs crosstalk through competitively binding to mi RNA via mi RNA response elements ( MREs) contained within the RNA sequences, thus forming a complex regulatory network. The ratio of a subset of mi RNAs to the corresponding number of MREs determines repression strength on a given mRNA translation or stability. An increase in pseudogene RNA level can sequester mi RNA 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 ce RNA network and biological significance of regulation.