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/.
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Project description:Background: Chronic hepatitis B (CHB) infection is a serious health problem worldwide and with the current treatment a functional cure is only achieved in 3-15% of the patients. Therefore it is important to investigate novel biomarkers for treatment outcome and to develop new treatment options for CHB. miRNAs are small, non-coding RNA molecules that are involved in various cellular processes by regulating gene expression at the posttranscriptional level and also play an important role in a variety of infectious diseases. In this study we want to identify novel miRNAs that are involved in hepatitis B replication and could therefore be used as biomarkers and targeted as a potential new therapeutic option. Methods: miRNA/small RNA NGS was performed on total RNA isolated from 10 matching plasma and liver biopsy of an identification cohort of CHB patients and 10 plasma and liver controls. Results: We identified 23 and 18 miRNAs that were differentially expressed between controls and CHB patients in plasma and liver respectively, of which five were differentially expressed in both liver and plasma. Of these candidate miRNAs 3 were upregulated in liver and 12 in plasma from CHB and 15 were downregulated in liver and 11 in plasma.
Project description:<p>There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis and monitoring disease progression. In this study we evaluated cerebrospinal fluid (CSF) proteins, which are known to be critically involved in PD or identified in our preliminary profiling studies, aptamers, and RNAs as potential PD biomarkers. Access to subjects for this study was via the Pacific Northwest Udall Center (PANUC) and the Alzheimer's Disease Research Center (ADRC) at the University of Washington and Oregon Health and Sciences University (OHSU). Using CSF samples from 30 well-characterized patients with PD and 30 age-, sex-matched healthy controls, we prepared RNA seq libraries and performed deep sequencing of all RNA species, including small and long RNA, mRNAs, noncoding RNAs and differentially spliced transcripts. We then tried several methods for RNAseq data analysis to optimize our analysis pipeline. We identified a total of 3381 transcripts corresponding to 182 long intergenic RNAs (LincRNAs), 11 microRNAs (miRNAs), 2861 protein-coding transcripts, 200 pseudogenes and 127 antisense RNAs; some of them were differentially expressed between PD and control groups. Selected differentially expressed RNAs have been validated in the same set of CSF samples using real-time PCR (RT-PCR). Further validations in independent, larger cohorts of samples are still ongoing. Our results obtained so far suggested that CSF proteins and RNAs could be used as good indexes for PD diagnosis and disease severity/progression. This study is a part of the NIDDS-funded Parkinson's Disease Biomarkers Program (PDBP).</p>
Project description:Background: MicroRNAs (miRNAs) represent a family of small endogenous, non-coding RNAs that play critical regulatory roles in plant growth, development, and environmental stress responses. Although Hami melon is an attractive model for valuable biological traits analysis, the role of miRNA action in the fruit development and ripening remains largely unknown. Here, we performed small RNA sequencing to investigate the Hami melon miRNA profiles at four fruit developmental stages Results: Small RNA sequencing yielded raw reads in eight libraries. miRNAs expression profiles were variable at different fruit developmental stages. The expression levels of five known miRNAs were validated by quantitative real-time PCR. Among the identified miRNAs, several miRNAs showed developmentally regulated and differentially expressed pattern during fruit development. Conclusions: Our results present a first comprehensive set of identification and characterization of Hami melon fruit miRNAs and their potential targets, which provide valuable basis for further research on the critical role of miRNAs in melon fruit development.
Project description:Pig is the important animal model for human obesity and diseases. However, the complexity of the porcine transcriptome is not yet fully elucidated. Here we have used massively parallel high-throughput sequencing of cDNA (RNA-seq) to generate a high-resolution map of the porcine miRNA in liver (LI), longissimus dorsi (LD) and abdominal fat (AF) from a F2 female full-sib pair with extreme phenotypes on growth and fat deposit. Through small RNA sequencing and on the basis of miRbase15.0, we detected a total of 184 mature miRNAs and 164 unique porcine novel miRNAs. Some conserved miRNAs, such as miR-122, miR-1, miR-206 and let-7 family showed high expression level in this study. Finally, we identified 10, 20 and 63 differentially expressed miRNAs, respectively, in LI, LD and AF. This high resolution and comprehensive transcriptome analysis significantly enhances the current genome annotation of pigs. examining the complexity of pig transcriptome in three organs from a female full-sib pair
Project description:Purpose: To reveal the cystogenesis regulatory mechanism by miRNA and miRNA targeted genes in ADPKD mouse models. Method(miRNA-seq): Small RNA sample preparation was done according to Illumina’s protocol. In brief, 5’ and 3’ adapters were sequentially ligated to small RNA of 18–30 bases gel purified from 5–10 µ total RNA. Adapter-ligated small RNA was reverse transcribed, amplified and sequenced on a HiSeq2000 (Illumina) following manufacturer's instructions. Raw data (the reads for each miRNA) were normalized to the total reads of each individual sample as the standardized to reads per (RPM; miRNA counts / total count of each sample x 1 million). Method(common): Both miRNA-seq and RNA-seq were carried out using the kidney tissues from two mouse models at postnatal day 1, 3 and 7 in triplicate samples. Total RNA was isolated using TRIzol method according to manufacturer’s protocol (Invitrogen Life Technologies). Result: UIn RNA-seq analysis, total 3,040 transcripts in Pkd1f/f:HoxB7-cre mice and 2,470 transcripts in Pkd2f/f:HoxB7-cre mice were differentially expressed at indicated time points (FDR<0.05). In addition, we also identified 1,297 common transcripts in both mouse models. In miRNA analysis, total 243 of miRNAs were identified as differentially expressed genes while 130 miRNAs were common in both mouse models. Among common miRNAs, total 13 miRNAs including 11 upregulated and 2 downregulated miRNAs were selected based on comparison of expression patterns at each time point. Conclusion: Our study described the parallel integrated analysis of miRNA-seq and RNA-seq data and validated the expression, direct interaction and cystogenesis-related functions of key miRNAs and mRNA targets.