Biology subjects

Marz, M.

Publications and source records attributed to Marz, M..

4 recordsLinked to original sources

bioRxiv2018

SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structural RNAs

BackgroundA single nucleotide change in the coding region can alter the amino acid sequence of a protein. In consequence, natural or artificial sequence changes in viral RNAs may have various effects not only on protein stability, function and structure but also on viral replication.\n\nIn recent decades, several tools have been developed to predict the effect of mutations in structured RNAs such as viral genomes or non-coding RNAs. Some tools use multiple point mutations and also take coding regions into account. However, none of these tools was designed to specifically simulate the effect of mutations on viral long-range interactions.\n\nResultsHere, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate disruptive and compensatory mutants of two interacting single-stranded RNAs. This allows a fast and accurate assessment of key regions potentially involved in functional long-range RNA-RNA interactions and will eventually help virologists and RNA-experts to design appropriate experiments.\n\nSIM only requires two interacting single-stranded RNA regions as input. The output is a plain text file containing the most promising mutants and a graphical representation of all interactions.\n\nConclusionWe applied our tool on two experimentally validated influenza A virus and hepatitis C virus interactions and we were able to predict potential double mutants for in vitro validation experiments.\n\nAvailabilityThe source code and documentation of SIM are freely available at github.com/desiro/silentMutations.

bioinformatics↗

bioRxiv2018

Identification of potential microRNAs associated with Herpesvirus family based on bioinformatic analysis

MicroRNAs (miRNAs) are known key regulators of gene expression on posttranscriptional level in many organisms encoded in mammals, plants and also several viral families. To date, no homologous gene of a virus-originated miRNA is known in other organisms. To date, only a few homologous miRNA between two different viruses are known, however, no gene of a virus-originated miRNA is known in any organism of other kingdoms. This can be attributed to the fact that classical miRNA detection approaches such as homology-based predictions fail at viruses due to their highly diverse genomes and their high mutation rate.\n\nHere, we applied the virus-derived precursor miRNA (pre-miRNA) prediction pipeline ViMiFi, which combines information about sequence conservation and machine learning-based approaches, on Human Herpesvirus 7 (HHV7) and Epstein-Barr virus (EBV). ViMiFi was able to predict 61 candidates in EBV, which has 25 known pre-miRNAs. From these 25, ViMiFi identified 20. It was further able to predict 18 candidates in the HHV7 genome, in which no miRNA had been described yet. We also studied the undescribed candidates of both viruses for potential functions and found similarities with human snRNAs and miRNAs from mammals and plants.

bioinformatics↗

bioRxiv2018

Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines

IntroductionLeukemia Inhibitory Factor (LIF) regulates behavior of trophoblast cells and their interaction with immune and endothelial cells. In vitro, trophoblast cell response to LIF may vary depending on the cell model. Reported differences in the miRNA profile of trophoblastic cells may be responsible for these observations. Therefore, miRNA expression was investigated in four trophoblastic cell lines under LIF stimulation followed by in silico analysis of altered miRNAs and their associated pathways.\n\nMethodsLow density TaqMan miRNA assays were used to quantify levels of 762 mature miRNAs under LIF stimulation in three choriocarcinoma-derived (JEG-3, ACH-3P and AC1-M59) and a trophoblast immortalized (HTR-8/SVneo) cell lines. Expression of selected miRNAs was confirmed in primary trophoblast cells and cell lines by qPCR. Targets and associated pathways of the differentially expressed miRNAs were inferred from the miRTarBase followed by a KEGG Pathway Enrichment Analysis. HTR-8/SVneo and JEG-3 cells were transfected with miR-21-mimics and expression of miR-21 targets was assessed by qPCR.\n\nResultsA similar number of miRNAs changed in each tested cell line upon LIF stimulation, however, low coincidence of individual miRNA species was observed and occurred more often among choriocarcinoma-derived cells (complete data set at http://www.ncbi.nlm.nih.gov/geo/ under GEO accession number GSE130489). Altered miRNAs were categorized into pathways involved in human diseases, cellular processes and signal transduction. Six cascades were identified as significantly enriched, including JAK/STAT and TGFB-SMAD. Upregulation of miR-21-3p was validated in all cell lines and primary cells and STAT3 was confirmed as its target.\n\nDiscussionDissimilar miRNA responses may be involved in differences of LIF effects on trophoblastic cell lines.

molecular biology↗

bioRxiv2017

A miRNA catalogue and ncRNA annotation of theshort-living fish Nothobranchius furzeri

Background: The short-lived fish Nothobranchius furzeri is the shortest-lived vertebrate that can be cultured in captivity and was recently established as a model organism for aging research. Small non-coding RNAs, especially miRNAs, are implicated in age-dependent control of gene expression.\n\nResults: Here, we present a comprehensive catalogue of miRNAs and several other non-coding RNA classes (ncRNAs) for Nothobranchius furzeri. Analyzing multiple small RNA-Seq libraries, we show most of these identified miRNAs are expressed in at least one of seven Nothobranchius species. Additionally, duplication and clustering of N. furzeri miRNAs was analyzed and compared to the four fish species Danio rerio, Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes. A peculiar characteristic of N. furzeri as compared to other teleosts was a duplication of the miR-29 cluster.\n\nConclusion: The completeness of the catalogue we provide is comparable to that of zebrafish. This catalogue represents a basis to investigate the role of miRNAs in aging and development in this species.\n\nAvailability: All supplementary material can be found online at http://www.rna.uni-jena.de/en/supplements/nothobranchius-furzeri-mirnome/.

genomics↗