Identification of a novel antisense noncoding RNA, ALID, transcribed from the putative imprinting control region of marsupial IGF2R

Abstract

BackgroundGenomic imprinting leads to maternal expression of IGF2R in both mouse and opossum. In mouse, the antisense long noncoding (lnc) RNA Airn, which is paternally expressed from the differentially methylated region (DMR) in the second intron of Igf2r, is required to silence the paternal Igf2r. In opossum, however, intriguingly, the DMR was reported to be in a different downstream intron (intron 11) and there was no antisense lncRNA detected in previous analyses. Therefore, clarifying the imprinting mechanism of marsupial IGF2R is of great relevance for understanding the origin and evolution of genomic imprinting in the IGF2R locus. Thus, the antisense lncRNA associated with the marsupial DMR can be considered as the ‘missing link’. In this study, we identified a novel antisense lncRNA, ALID, after detailed analysis of the IGF2R locus in an Australian marsupial, the tammar wallaby, Macropus eugenii, and compared it to that of the grey short-tailed opossum, Monodelphis domestica.ResultsTammar IGF2R showed maternal expression and had a maternally methylated CpG island (CGI) in intron 12 as well as a promoter CGI without differential methylation, but none in the second intron. Re-analysis of the IGF2R of opossum detected the CGI in intron 12, not intron 11, as previously reported, confirming that the DMR in intron 12 is conserved between these marsupials and so is the putative imprinting control region of marsupial IGF2R. ALID is paternally expressed from the middle of the DMR and is approximately 650 bp long with a single exon structure that is extremely short compared to Airn. Hence, the lncRNA transcriptional overlap of the IGF2R promoter, which is essential for the Igf2r silencing in the mouse, is likely absent in tammar. This suggests that fundamental differences in the lncRNA-based silencing mechanisms evolved in eutherian and marsupial IGF2R and may reflect the lack of differential methylation in the promoter CGI of marsupial IGF2R.ConclusionsOur study thus provides the best candidate factor for establishing paternal silencing of marsupial IGF2R without transcriptional overlap, which is distinct from the Igf2r silencing mechanism of Airn, but which may be analogous to the mode of action for the flanking Slc22a2 and Slc22a3 gene silencing in the mouse placenta.Electronic supplementary materialThe online version of this article (10.1186/s13072-018-0227-8) contains supplementary material, which is available to authorized users.

WOMEN IN REPRODUCTIVE SCIENCE: Reproduction down under

“…Most recently, continuing our collaboration with Shunsuke Suzuki we showed that there is a lncRNA (ALID) in the marsupial IFG2R locus. This gene is the best candidate factor for establishing the paternal silencing of marsupial IGF2R but without the transcriptional overlap that occurs in the mouse Ifg2r locus with its lncRNA Airn (Suzuki et al 2018). The tammar also shares the same process of global methylation of germ cells as other mammals, although as expected, the timing differs, being postnatal in the tammar and pre-natal in eutherians (Ishihara et al 2019).…”

LncRNA Malat1 regulates iPSC-derived β-cell differentiation by targeting the miR-15b-5p/Ihh axis

“…As research has progressed, ncRNAs such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been found to participate in cellular signalling and regulation of various processes [9][10][11]. In recent years, as transcripts have been shown to exceed 200 bp, lncRNAs have been proven to control gene regulation, organ differentiation and both developmental and pathological processes [12][13][14]. Moreover, studies have indicated that lncRNAs participate in pancreatic and islet development, β-cell formation and function and T cell differentiation in vitro [15][16][17][18].…”

Genetic and genomic architecture in eight strains of the laboratory opossumMonodelphis domestica

“…For example, opossum pups are born on embryonic day 14, at the same stage of a 6-week human embryo or E11.5 mouse embryo, which enables many kinds of early embryonic studies that cannot be easily conducted with eutherians, in which access to embryos and fetuses at these stages requires considerable disruption of the gestational environment (Cardoso-Moreira et al 2019; Mahadevaiah et al 2020). Marsupials are also valuable for investigating major epigenetic processes such as X-chromosome inactivation (Hornecker et al 2007; Grant et al 2012; Rodriguez-Delgado et al 2014; Wang et al 2014; Waters et al 2018; Mahadevaiah et al 2020) and genomic imprinting (Weidman et al 2006; Lawton et al 2008; Das et al 2012; Douglas et al 2014; Suzuki et al 2018). M. domestica has been used in many medical and disease studies, such as gene expression during neural development (Dooley et al 2012; Sears et al 2012; Pavan et al 2014; Wheaton et al 2021), hypercholesterolemia and steatohepatitis (Chan et al 2010; Chan and VandeBerg 2011; Chan et al 2012), cancer therapy and prevention (Nair and VandeBerg 2012; Nair et al 2014), immunogenomics (Parra et al 2008; Morrissey et al 2021; Schraven et al 2021), viral pathogenesis (Thomas et al 2019), and influence of biological sex on social behavior, individual recognition, and associative learning (Gil et al 2019).…”