The Evolution of Imprinted microRNAs and Their RNA Targets

Abstract

Mammalian genomes contain many imprinted microRNAs. When an imprinted miRNA targets an unimprinted mRNA their interaction may have different fitness consequences for the loci encoding the miRNA and mRNA. In one possible outcome, the mRNA sequence evolves to evade regulation by the miRNA by a simple change of target sequence. Such a response is unavailable if the targeted sequence is strongly constrained by other functions. In these cases, the mRNA evolves to accommodate regulation by the imprinted miRNA. These evolutionary dynamics are illustrated using the examples of the imprinted C19MC cluster of miRNAs in primates and C2MC cluster in mice that are paternally expressed in placentas. The 3′ UTR of PTEN, a gene with growth-related and metabolic functions, appears to be an important target of miRNAs from both clusters.

Essential Role of the 14q32 Encoded miRNAs in Endocrine Tumors

“…The evolutional role and constraint can be considered another point of view of imprinted miRNAs [ 184 , 185 , 186 ]. It was suggested that imprinted noncoding RNAs was under distinctive selective forces when regulating transcripts of the allele inherited from the other parent [ 184 , 185 , 186 , 187 ]. Accordingly, when an mRNA had sequence complementary to an imprinted miRNA, the complementary miRNA-mRNA sequences pair originated from different alleles.…”

“…This can be considered a communication between the maternal and paternal alleles, hence the two alleles coordinate their activities [ 186 ]. The kinship theory considers genomic imprinting as a mechanism to change gene dosage, because it has a differential effect on the fitness of matrilineal and patrilineal relatives [ 184 , 185 , 186 , 187 ]. Additionally, Haig and Mainieri suggested that when an imprinted miRNA targets an unimprinted mRNA, their interaction may have different fitness consequences for the loci encoding the miRNA and mRNA [ 184 ].…”

“…The kinship theory considers genomic imprinting as a mechanism to change gene dosage, because it has a differential effect on the fitness of matrilineal and patrilineal relatives [ 184 , 185 , 186 , 187 ]. Additionally, Haig and Mainieri suggested that when an imprinted miRNA targets an unimprinted mRNA, their interaction may have different fitness consequences for the loci encoding the miRNA and mRNA [ 184 ]. In a recent study, HMGA2 was proposed as an attractive candidate to be one of the original targets because its 3′ regulatory region contained multiple predicted target sites for 14q32 miRNAs, with some of these target sites evolutionarily older than the 14q32 miRNA cluster [ 184 ].…”

“…Additionally, Haig and Mainieri suggested that when an imprinted miRNA targets an unimprinted mRNA, their interaction may have different fitness consequences for the loci encoding the miRNA and mRNA [ 184 ]. In a recent study, HMGA2 was proposed as an attractive candidate to be one of the original targets because its 3′ regulatory region contained multiple predicted target sites for 14q32 miRNAs, with some of these target sites evolutionarily older than the 14q32 miRNA cluster [ 184 ]. HMGA2 have special role in this context as it has reported to be overexpressed in several cancer type including endocrine tumors and often regulated by miRNAs [ 188 , 189 ], which also highlights the role of 14q32 miRNAs in tumorigenesis.…”

A Textual Deconstruction of the RNA World

“…Proteins are a more expressive language than RNA. However, this relegation of RNA to the role of a messenger between DNA text and protein performance neglects the central roles that ‘non-coding’ RNAs continue to play in information-processing within cells (Mainieri & Haig, 2018 , 2019 ; Haig & Mainieri, 2020 ).…”