MicroRNA evolution in placental mammals: Unravelling conservation and divergence in their regulatory mechanisms in early pregnancy in different placen

点击翻译按钮获取中文摘要

Background:In eutherian mammals, the emergence of the placenta as an organ was coordinate with the emergence of novel regulatory mechanisms in the genome. Once such example is a specific cohort of microRNAs (miRNAs) at the stem lineage of placental mammals. miRNAs play an important role in uterine endometrial and placental function to establish successful pregnancy. It is unclear however, how conserved or diverse the regulatory mechanisms of these placental mammal-specific miRNAs are and if they regulate the placenta as an organ itself or some other aspect of placental mammal physiology.Objectives:1-To determine the expression of novel placental mammal-specific miRNAs and their predicted targets in placental mammal-specific tissues (endometrium, placenta, mammary gland) from different species. 2-To investigate if candidate miRNAs regulate gene expression in a divergent or conserved manner via knockdown or overexpression of miRNA's in in vitro. 3-To determine if candidate miRNA (s) regulate the same or different processes in the same species i.e. mammary gland or placental specific regulation of gene expression. Novelty:This cutting-edge project combines uterine and placental biology, miRNA regulation and computational evolutionary biology to address how miRNAs contributed to the emergence of placental mammals and placental diversity.Timeliness:The project will focus on 14 microRNA's that arose specifically in the common ancestor of all placental mammals - novel unpublished data generated by a PhD student co-supervised by Dr Forde and Dr O'Connell, as well as placental mammal phylogeny which has recently been published by Dr O'Connell et al. Experimental Approaches: Candidate miRNA and target expression will be assessed in endometrial, placental and mammary gland tissues from species representing distinctive placental morphologies including bovine, porcine, feline, rodent, and marsupials. Functional analysis will be validated by in vitro knock down/addition of miRNA mimics to in vitro cell lines and effects measured by RNAseq and/or nano-LC MS/MS.