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Overexpression of Mir-197 und Mir-769 in human iPSCs

ABSTRACT: MicroRNAs (miRNAs) are post-transcriptional regulators that are involved in many essential biological processes. Recently, targeted searches for human miRNA orthologs revealed that 15 miRNA families are lost in the Eumuroidea lineage, including the model organisms mouse and rat, but not in other mammals. We here characterize this loss in more detail and investigate potential consequences for the Eumuroidean regulatory network. We confirm that the miRNA loss was not compensated by other miRNAs in rat or mouse, and we identify a significant overlap in the function of their target genes. We heterologously express two human miRNAs, Mir-197 and Mir-769, in mouse inducible pluripotent stem cells (iPSCs) and compare effects on the transcriptome to those of induced miRNA levels in human iPSCs. This reveals overlapping sets of down-regulated mRNAs in the two species, likely representing remnants of an ancient miRNA-dependent regulatory network that predates the diversification of the human and mouse lineages. The consequent elimination of established miRNA regulatory connections on the Eumuroidean lineage is accompanied by the lineage-specific loss of 37 transcription factors. Our results indicate that mouse and rat have modified their regulatory network of gene expression on transcriptional and post-transcriptional level compared to other vertebrate model organisms. This regulatory shift likely adds noise to studies of gene expression that, for example, use murine cells to study human diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281793 | GEO | 2025/06/04

REPOSITORIES: GEO

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Project description:Schmitz2014 - RNA triplex formation The model is parameterized using the parameters for gene CCDC3 from Supplementary Table S1. The two miRNAs which form the triplex together with CCDC3 are miR-551b and miR-138. This model is described in the article: Cooperative gene regulation by microRNA pairs and their identification using a computational workflow. Schmitz U, Lai X, Winter F, Wolkenhauer O, Vera J, Gupta SK. Nucleic Acids Res. 2014 Jul; 42(12): 7539-7552 Abstract: MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergize and which genes are target of cooperative miRNA regulation. In this paper, we present a computational workflow for the prediction and analysis of cooperating miRNAs and their mutual target genes, which we refer to as RNA triplexes. The workflow integrates methods of miRNA target prediction; triplex structure analysis; molecular dynamics simulations and mathematical modeling for a reliable prediction of functional RNA triplexes and target repression efficiency. In a case study we analyzed the human genome and identified several thousand targets of cooperative gene regulation. Our results suggest that miRNA cooperativity is a frequent mechanism for an enhanced target repression by pairs of miRNAs facilitating distinctive and fine-tuned target gene expression patterns. Human RNA triplexes predicted and characterized in this study are organized in a web resource at www.sbi.uni-rostock.de/triplexrna/. This model is hosted on BioModels Database and identified by: BIOMD0000000530. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Overexpression of Mir-197 und Mir-769 in human iPSCs

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