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Identification and characterization of microRNAs (miRNAs) and their transposable element origins in the saltwater crocodile, Crocodylus porosus

ABSTRACT: MicroRNAs (miRNAs) are 18-24 nucleotide autonomous regulatory RNA molecules found in all eukaryotes. They are involved in the regulation of a multitude of genetic and biological pathways through post transcriptional gene silencing and/or translational repression. Previous data has suggested a slow evolutionary rate for the saltwater crocodile (Crocodylus porosus) over the past several million years when compared to its closest extant relatives, the birds. Understanding genome regulation, adaptive capabilities and physiological features in the saltwater crocodile in the context of relatively slow genomic change thus holds significant potential for the investigation of genomics, evolution and adaptive studies. Utilizing eleven different tissue types and sixteen small RNA libraries, we report a catalog of 644 miRNAs in the saltwater crocodile with > 78% of miRNAs being potentially novel to crocodilians. We also predicted and identified targets for the miRNAs as well as analyzed the relationship of the miRNA repertoire to transposable elements (TEs) in the saltwater crocodile that showed an increased association of DNA transposons with miRNA biogenesis when compared to retrotransposons. Phylogenetic analysis of C. porosus miRNA expectedly revealed highest number of miRNAs in sister crocodilian clades of the American Alligator and the Indian Gharial. This work reports the first comprehensive analysis of miRNAs in Crocodylus porosus for and addresses the potential impacts of miRNAs in regulating the genome in the saltwater crocodile as well as supporting the role of TEs as a source for miRNAs, adding to the increasing evidence that TEs play a significant role in the evolution of gene regulation.

ORGANISM(S): Crocodylus porosus

PROVIDER: GSE150461 | GEO | 2020/08/24

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.

Project description:Recurrent hepatitis C virus (rHCV) is universal post-liver transplantation (LT), with accelerated fibrosis rates compared to non-transplanted patients. rHCV is associated with increased mortality and morbidity post-transplant and is a leading indication for re-transplantation. We hypothesized that miRNA expression profiles from liver grafts can distinguish severity of HCV recurrence and differentiate this from acute cellular rejection (ACR). Methods Using microarrays, we characterized global microRNA (miRNA) expression from patients with slow HCV fibrosis progression (F<2 Ishak), fast HCV fibrosis progression (FM-bM-^IM-%2 Ishak), ACR and non-HCV transplanted patients. Selected miRNA were analysed by quantitative PCR (qPCR) using both liver tissue and serum samples. Results We demonstrated changes in miRNA expression in patients with slow HCV fibrosis progression that were anti-fibrogenic, anti-angiogenic and anti-inflammatory in comparison to patients with fast HCV fibrosis progression. miRNA-146a, miRNA-19a, miRNA- 20a and miRNA-let-7e expression were increased in the slow HCV fibrosis progression group. In addition, comparison of patients with fast HCV progression against patients with ACR identified pro-fibrogenic pathways. qPCR analysis on liver tissue and serum confirmed the up-regulation of miRNAs in the slow HCV fibrosis progression group. Conclusion We demonstrate specific miRNA expression signatures that distinguish rate of progression of HCV recurrence and ACR post M-bM-^@M-^Sliver transplantation. Pathway analysis indicates that specific miRNA may play a regulatory role in these processes. The miRNAs identified may act as potential biomarkers for HCV recurrence post-LT and help distinguish between ACR and recurrent HCV. We compared 29 patients in total; 11 patients with slow HCV fibrosis progression, 9 patients with fast HCV fibrosis progression, 5 patients with acute cellular rejection and 4 HCV negative patients with normal liver histology that acted as controls. RNA was extracted from archived histology samples of the RG and NRG and miRNA expression was analysed using the affymetrix Genechip miRNA 2.0 assays.

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Identification and characterization of microRNAs (miRNAs) and their transposable element origins in the saltwater crocodile, Crocodylus porosus

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