Retroposition as a source of antisense long non-coding RNAs with possible regulatory functions

Long non-coding RNAs (lncRNAs) are a class of intensely studied, yet enigmatic molecules that make up a substantial portion of the human transcriptome. In this work, researchers from Adam Mickiewicz University in Poznan link the origins and functions of some lncRNAs to retroposition, a process resulting in the creation of intronless copies (retrocopies) of the so-called parental genes. They found 35 human retrocopies transcribed in antisense and giving rise to 58 lncRNA transcripts. These lncRNAs share sequence similarity with the corresponding parental genes but in the sense/antisense orientation, meaning they have the potential to interact with each other and to form RNA:RNA duplexes. The researchers took a closer look at these duplexes and found that 10 of the lncRNAs might regulate parental gene expression and processing at the pre-mRNA and mRNA levels. Further analysis of the co-expression and expression correlation provided support for the existence of functional coupling between lncRNAs and their mate parental gene transcripts.

(A) Schematic representation of the retroposition process. (B) Mechanism behind the creation of lncRNA base-pairings with parental genes at the mRNA level. Once a retrocopy is transcribed in the antisense orientation, the resulting lncRNAs share sequence similarity with the parental genes in the sense/antisense orientation, meaning they are able to interact and form RNA:RNA duplexes with possible regulatory implications. (C) Evolutionary mechanism that enables the formation of lncRNA interactions with the pre-mRNAs of parental genes. A retrocopy is created from one of many splice forms of the parental gene. Its antisense lncRNAs are complementary to the pre-mRNAs of the parental gene. Although retrocopies typically are devoid of introns, some of the retroposition-derived lncRNAs are able to basepair with intronic parts of the parental gene’s pre-mRNAs and mask the intronic splicing signals. This is possible if the process of retroposition and the formation of lncRNA:RNA duplexes engages different splice forms of the parental gene, as shown in the figure.