Conservation and novelty in the microRNA genomic landscape of hyperdiverse cichlid fishes

Abstract MicroRNAs (miRNAs) play crucial roles in the post-transcriptional control of messenger RNA (mRNA). These miRNA-mRNA regulatory networks are present in nearly all organisms and contribute to development, phenotypic divergence, and speciation. To examine the miRNA landscape of cichlid fishes, one of the most species-rich families of vertebrates, we profiled the expression of both miRNA and mRNA in a diverse set of cichlid lineages. Among these, we found that conserved miRNAs differ from recently arisen miRNAs (i.e. lineage specific) in average expression levels, number of target sites, sequence variability, and physical clustering patterns in the genome. Furthermore, conserved miRNA target sites tend to be enriched at the 5′ end of protein-coding gene 3′ UTRs. Consistent with the presumed regulatory role of miRNAs, we detected more negative correlations between the expression of miRNA-mRNA functional pairs than in random pairings. Finally, we provide evidence that novel miRNA targets sites are enriched in genes involved in protein synthesis pathways. Our results show how conserved and evolutionarily novel miRNAs differ in their contribution to the genomic landscape and highlight their particular evolutionary roles in the adaptive diversification of cichlids.

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Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-93531-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hibah Shaath ◽

Salman M. Toor ◽

Mohamed Abu Nada ◽

Eyad Elkord ◽

Nehad M. Alajez

Keyword(s):

Colorectal Cancer ◽

Messenger Rna ◽

Regulatory Networks ◽

Potential Interaction ◽

Therapeutic Interventions ◽

Signaling Networks ◽

Protein Coding ◽

Paired Samples ◽

And Migration ◽

Whole Transcriptome

AbstractColorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC.

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Parallel analysis of miRNAs and mRNAs suggests distinct regulatory networks in Crassostrea gigas infected by Ostreid herpesvirus 1

BMC Genomics ◽

10.1186/s12864-020-07026-7 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Umberto Rosani ◽

Miriam Abbadi ◽

Timothy Green ◽

Chang-Ming Bai ◽

Edoardo Turolla ◽

...

Keyword(s):

Crassostrea Gigas ◽

Messenger Rna ◽

Regulatory Networks ◽

Viral Infections ◽

Degradation Products ◽

Differentially Expressed ◽

Protein Coding ◽

Functional Studies ◽

Herpesvirus 1 ◽

Ostreid Herpesvirus 1

Abstract Background Since 2008, the aquaculture production of Crassostrea gigas was heavily affected by mass mortalities associated to Ostreid herpesvirus 1 (OsHV-1) microvariants worldwide. Transcriptomic studies revealed the major antiviral pathways of the oyster immune response while other findings suggested that also small non-coding RNAs (sncRNA) such as microRNAs might act as key regulators of the oyster response against OsHV-1. To explore the explicit connection between small non-coding and protein-coding transcripts, we performed paired whole transcriptome analysis of sncRNA and messenger RNA (mRNA) in six oysters selected for different intensities of OsHV-1 infection. Results The mRNA profiles of the naturally infected oysters were mostly governed by the transcriptional activity of OsHV-1, with several differentially expressed genes mapping to the interferon, toll, apoptosis, and pro-PO pathways. In contrast, miRNA profiles suggested more complex regulatory mechanisms, with 15 differentially expressed miRNAs (DE-miRNA) pointing to a possible modulation of the host response during OsHV-1 infection. We predicted 68 interactions between DE-miRNAs and oyster 3′-UTRs, but only few of them involved antiviral genes. The sncRNA reads assigned to OsHV-1 rather resembled mRNA degradation products, suggesting the absence of genuine viral miRNAs. Conclusions We provided data describing the miRNAome during OsHV-1 infection in C. gigas. This information can be used to understand the role of miRNAs in healthy and diseased oysters, to identify new targets for functional studies and, eventually to disentangle cause and effect relationships during viral infections in marine mollusks.

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Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

BioMed Research International ◽

10.1155/2016/5469371 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Jianghong Wu ◽

Husile Gong ◽

Yongsheng Bai ◽

Wenguang Zhang

Keyword(s):

Gene Networks ◽

Regulatory Networks ◽

Mirna Gene ◽

Genetic Regulatory Networks ◽

Host Immunity ◽

Genetic Networks ◽

Target Sites ◽

Enormous Number ◽

Human And Mouse

Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore,hsa-miR-548,mmu-miR-466, andmmu-miR-467have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse.

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Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis

10.21203/rs.2.10525/v1 ◽

2019 ◽

Author(s):

Xiao Ma ◽

Shuangshuang Cen ◽

Luming Wang ◽

Chao Zhang ◽

Limin Wu ◽

...

Keyword(s):

Messenger Rna ◽

Regulatory Networks ◽

Target Genes ◽

Expression Profiles ◽

Integrated Analysis ◽

Regulation Mechanism ◽

Pelodiscus Sinensis ◽

Specific Expression ◽

Protein Coding ◽

Protein Coding Genes

Abstract Abstract Background: Gonad is the major factor affecting the animal reproduction. The regulation mechanism of protein coding genes expression involved reproduction is still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction had been investigated in some species. However, the regulation patterns of miRNA and lncRNA in sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of the soft-shelled turtle, Pelodiscus sinensis. Results: We identified 10 796 mature miRNAs, 44 678 mRNAs, and 58 923 lncRNAs in the testis and ovary. A total of 16 817 target genes were identified for miRNAs. Of these, 11 319 mRNAs, 10 495 lncRNAs, and 633 miRNAs were expressed differently. The predicted target genes of these differential expression (DE) miRNAs and lncRNAs included genes related to reproduction regulation. Furthermore, we found that 5 408 DElncRNAs and 186 DE miRNAs showed sex-specific expression. Of these, 3 miRNAs and 917 lncRNAs were testis specific and 186 DEmiRNAs and 4 491 DElncRNAs were ovary specific. We constructed compete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 273 DEmRNAs, 5 730 DEmiRNAs, and 2 945 DElncRNAs. The target genes for the different expressed of miRNAs and lncRNAs included Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1, etc. Conclusions: In animals, miRNA and lncRNA regulate the reproduction process, including the regulation of oocyte maturation and spermatogenesis. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproduction traits for aquaculture.

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Making a mark: the role of RNA modifications in plant biology

The Biochemist ◽

10.1042/bio20200046 ◽

2020 ◽

Vol 42 (4) ◽

pp. 26-30

Author(s):

Matthew T. Parker ◽

Katarzyna Knop ◽

Gordon G. Simpson

Keyword(s):

Messenger Rna ◽

Growth And Development ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Biological Significance ◽

Plant Biology ◽

Developmental Pathways ◽

Rna Modifications ◽

Feature Article

Plants coordinate their growth and development through complex regulatory networks involving changes in the expression of thousands of genes. Many developmental pathways are regulated at the level of messenger RNA (mRNA) through alternative choices in mRNA processing. These choices can have consequences for the localization, stability or translatability of mRNAs. One of the key ways in which RNAs are processed is by the methylation of the RNA base adenosine – a modification known as m6A. Even though it was first discovered in the 1970s, the biological significance of m6A marks has only recently become clear. In this feature article, we identify the factors controlling the writing and reading of m6A modifications in plants. We also highlight some of the features of plant development that depend on m6A and explore the recently discovered molecular mechanisms that use m6A to control development or response to environmental stress.

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The β-Cell Genomic Landscape in T1D: Implications for Disease Pathogenesis

Current Diabetes Reports ◽

10.1007/s11892-020-01370-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mireia Ramos-Rodríguez ◽

Beatriz Pérez-González ◽

Lorenzo Pasquali

Keyword(s):

Regulatory Networks ◽

Current Knowledge ◽

Active Role ◽

Cell Types ◽

Β Cells ◽

Β Cell ◽

Risk Variants ◽

Genomic Landscape ◽

External Stimuli

Abstract Purpose of Review Type 1 diabetes (T1D) develops as a consequence of a combination of genetic predisposition and environmental factors. Combined, these events trigger an autoimmune disease that results in progressive loss of pancreatic β cells, leading to insulin deficiency. This article reviews the current knowledge on the genetics of T1D with a specific focus on genetic variation in pancreatic islet regulatory networks and its implication to T1D risk and disease development. Recent Findings Accumulating evidence suggest an active role of β cells in T1D pathogenesis. Based on such observation several studies aimed in mapping T1D risk variants acting at the β cell level. Such studies unravel T1D risk loci shared with type 2 diabetes (T2D) and T1D risk variants potentially interfering with β-cell responses to external stimuli. Summary The characterization of regulatory genomics maps of disease-relevant states and cell types can be used to elucidate the mechanistic role of β cells in the pathogenesis of T1D.

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RegAB Homolog of Burkholderia pseudomallei is the Master Regulator of Redox Control and involved in Virulence

PLoS Pathogens ◽

10.1371/journal.ppat.1009604 ◽

2021 ◽

Vol 17 (5) ◽

pp. e1009604

Author(s):

Julia Phenn ◽

Jan Pané-Farré ◽

Nikolai Meukow ◽

Annelie Klein ◽

Anne Troitzsch ◽

...

Keyword(s):

Burkholderia Pseudomallei ◽

Regulatory Networks ◽

Transcriptional Control ◽

Anaerobic Growth ◽

Infection Model ◽

Master Regulator ◽

Hypoxic Conditions ◽

Mouse Infection Model ◽

Denitrification Process

Burkholderia pseudomallei, the etiological agent of melioidosis in humans and animals, often occupies environmental niches and infection sites characterized by limited concentrations of oxygen. Versatile genomic features enable this pathogen to maintain its physiology and virulence under hypoxia, but the crucial regulatory networks employed to switch from oxygen dependent respiration to alternative terminal electron acceptors (TEA) like nitrate, remains poorly understood. Here, we combined a Tn5 transposon mutagenesis screen and an anaerobic growth screen to identify a two-component signal transduction system with homology to RegAB. We show that RegAB is not only essential for anaerobic growth, but also for full virulence in cell lines and a mouse infection model. Further investigations of the RegAB regulon, using a global transcriptomic approach, identified 20 additional regulators under transcriptional control of RegAB, indicating a superordinate role of RegAB in the B. pseudomallei anaerobiosis regulatory network. Of the 20 identified regulators, NarX/L and a FNR homolog were selected for further analyses and a role in adaptation to anaerobic conditions was demonstrated. Growth experiments identified nitrate and intermediates of the denitrification process as the likely signal activateing RegAB, NarX/L, and probably of the downstream regulators Dnr or NsrR homologs. While deletions of individual genes involved in the denitrification process demonstrated their important role in anaerobic fitness, they showed no effect on virulence. This further highlights the central role of RegAB as the master regulator of anaerobic metabolism in B. pseudomallei and that the complete RegAB-mediated response is required to achieve full virulence. In summary, our analysis of the RegAB-dependent modulon and its interconnected regulons revealed a key role for RegAB of B. pseudomallei in the coordination of the response to hypoxic conditions and virulence, in the environment and the host.

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Selection against maternal microRNA target sites in maternal transcripts

10.1101/012757 ◽

2014 ◽

Cited By ~ 1

Author(s):

Antonio Marco

Keyword(s):

Small Rnas ◽

Early Embryo ◽

Microrna Target ◽

Protein Coding ◽

Functional Impact ◽

Rna Molecules ◽

Target Sites ◽

Maternal Transcripts ◽

Gene Transcripts

In animals, before the zygotic genome is expressed, the egg already contains gene products deposited by the mother. These maternal products are crucial during the initial steps of development. In Drosophila melanogaster a large number of maternal products are found in the oocyte, some of which are indispensable. Many of these products are RNA molecules, such as gene transcripts and ribosomal RNAs. Recently, microRNAs ? small RNA gene regulators ? have been detected early during development and are important in these initial steps. The presence of some microRNAs in unfertilized eggs has been reported, but whether they have a functional impact in the egg or early embryo has not being explored. I have extracted and sequenced small RNAs from Drosophila unfertilized eggs. The unfertilized egg is rich in small RNAs and contains multiple microRNA products. Maternal microRNAs are often encoded within the intron of maternal genes, suggesting that many maternal microRNAs are the product of transcriptional hitch-hiking. Comparative genomics analyses suggest that maternal transcripts tend to avoid target sites for maternal microRNAs. I also developed a microRNA target mutation model to study the functional impact of polymorphisms at microRNA target sites. The analysis of Drosophila populations suggests that there is selection against maternal microRNA target sites in maternal transcripts. A potential role of the maternal microRNA mir-9c in maternal-to-zygotic transition is also discussed. In conclusion, maternal microRNAs in Drosophila have a functional impact in maternal protein-coding transcripts.

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