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      Genome-Wide Network of lncRNA–mRNA During Ovine Oocyte Development From Germinal Vesicle to Metaphase II in vitro

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          Abstract

          Long non-coding RNA (lncRNA) is involved in many biological processes, and it has been closely investigated. However, research into the role of lncRNA in ovine ovarian development is scant and poorly understood, particularly in relation to the molecular mechanisms of ovine oocyte maturation. In the current study, RNA sequencing was performed with germinal vesicle (GV) and in vitro matured metaphase II (MII) stage oocytes, isolated from ewes. Through the use of bioinformatic analysis, abundant candidate lncRNAs in stage-specific ovine oocytes were identified, and their trans- and cis-regulatory effects were deeply dissected using computational prediction software. Functional enrichment analysis of these lncRNAs revealed that they were involved in the regulation of many key signaling pathways during ovine oocyte development, which was reflected by their targeted genes. From this study, multiple lncRNA–mRNA networks were presumed to be involved in key signaling pathways regarding ovine oocyte maturation and meiotic resumption. In particular, one novel lncRNA (MSTRG.17927) appeared to mediate the regulation of phosphatidylinositol 3-kinase signaling (PI3K) signaling during ovine oocyte maturation. Therefore, this research offers novel insights into the molecular mechanisms underlying ovine oocyte meiotic maturation regulated by lncRNA–mRNA networks from a genome-wide perspective.

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          Most cited references45

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          The transcriptional landscape of the mammalian genome.

          This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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            Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.

            The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincRNAs are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincRNA (lincRNA-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincRNAs in the derivation of pluripotent stem cells.
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              The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin.

              A number of large noncoding RNAs (ncRNAs) epigenetically silence genes through unknown mechanisms. The Air ncRNA is imprinted--monoallelically expressed from the paternal allele. Air is required for allele-specific silencing of the cis-linked Slc22a3, Slc22a2, and Igf2r genes in mouse placenta. We show that Air interacts with the Slc22a3 promoter chromatin and the H3K9 histone methyltransferase G9a in placenta. Air accumulates at the Slc22a3 promoter in correlation with localized H3K9 methylation and transcriptional repression. Genetic ablation of G9a results in nonimprinted, biallelic transcription of Slc22a3. Truncated Air fails to accumulate at the Slc22a3 promoter, which results in reduced G9a recruitment and biallelic transcription. Our results suggest that Air, and potentially other large ncRNAs, target repressive histone-modifying activities through molecular interaction with specific chromatin domains to epigenetically silence transcription.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                18 August 2020
                2020
                : 11
                : 1019
                Affiliations
                [1] 1Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resource Conservation and Bio-breeding, College of Animal Science and Technology, Anhui Agricultural University , Hefei, China
                [2] 2Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Life Sciences, Qingdao Agricultural University , Qingdao, China
                [3] 3State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University , Hohhot, China
                Author notes

                Edited by: Kui Liu, The University of Hong Kong, Hong Kong

                Reviewed by: Yimin Zhu, Zhejiang University School of Medicine, China; Huan Shen, Peking University, China

                This article was submitted to Reproduction, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2020.01019
                7461901
                32973554
                885799c9-76d2-4797-aefb-3f55ae9b4405
                Copyright © 2020 Wang, Niu, Zhang, Shen and Cao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 April 2020
                : 24 July 2020
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 69, Pages: 12, Words: 0
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                lncrna–mrna network,ewe,oocytes,meiotic maturation,rna-seq
                Anatomy & Physiology
                lncrna–mrna network, ewe, oocytes, meiotic maturation, rna-seq

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