scholarly journals Detecting significant features in modeling microRNA-target interactions

Author(s):  
Claudia Coronnello ◽  
Giovanni Perconti ◽  
Patrizia Rubino ◽  
Flavia Contino ◽  
Serena Bivona ◽  
...  

MicroRNAs (miRNAs) are small non-coding RNA molecules mediating the translational repression and degradation of target mRNAs in the cell. Mature miRNAs are used as a template by the RNA-induced silencing complex (RISC) to recognize the complementary mRNAs to be regulated. Up to 60% of human genes are putative targets of one or more miRNAs. Several prediction tools are available to suggest putative miRNA targets, however, only a small part of the interaction pairs has been validated by experimental approaches. The analysis of the expression profile of the RNA fraction immunoprecipitated (IP) with the RISC proteins is an established method to detect which genes are actually regulated by the RISC machinery. In fact, genes that result over-expressed in the IP sample with respect to the whole cell lysate RNA, are considered as involved in the RISC complex, then miRNA targets. Here, we aim to find the features useful to predict which genes are overexpressed in IP, i.e. miRNA targets, without actually performing the IP experiments. To this purpose, we compiled and analyzed a novel high throughput data set suitable to unravel the features involved in the miRNA regulatory activities. We analyzed IP samples obtained by the immunoprecipitation of two RISC proteins, AGO2 and GW182. The two proteins shows different behaviors, in terms of enriched genes and features characterizing the immunoprecipitated RNA fractio. Further analysis is needed to unravel the reason of such different behavior.

2017 ◽  
Author(s):  
Claudia Coronnello ◽  
Giovanni Perconti ◽  
Patrizia Rubino ◽  
Flavia Contino ◽  
Serena Bivona ◽  
...  

MicroRNAs (miRNAs) are small non-coding RNA molecules mediating the translational repression and degradation of target mRNAs in the cell. Mature miRNAs are used as a template by the RNA-induced silencing complex (RISC) to recognize the complementary mRNAs to be regulated. Up to 60% of human genes are putative targets of one or more miRNAs. Several prediction tools are available to suggest putative miRNA targets, however, only a small part of the interaction pairs has been validated by experimental approaches. The analysis of the expression profile of the RNA fraction immunoprecipitated (IP) with the RISC proteins is an established method to detect which genes are actually regulated by the RISC machinery. In fact, genes that result over-expressed in the IP sample with respect to the whole cell lysate RNA, are considered as involved in the RISC complex, then miRNA targets. Here, we aim to find the features useful to predict which genes are overexpressed in IP, i.e. miRNA targets, without actually performing the IP experiments. To this purpose, we compiled and analyzed a novel high throughput data set suitable to unravel the features involved in the miRNA regulatory activities. We analyzed IP samples obtained by the immunoprecipitation of two RISC proteins, AGO2 and GW182. The two proteins shows different behaviors, in terms of enriched genes and features characterizing the immunoprecipitated RNA fractio. Further analysis is needed to unravel the reason of such different behavior.


2020 ◽  
Author(s):  
Fabian Kern ◽  
Jeremy Amand ◽  
Ilya Senatorov ◽  
Alina Isakova ◽  
Christina Backes ◽  
...  

AbstractArm selection, the preferential expression of a 3′ or 5′ mature microRNA (miRNA), is a highly dynamic and tissue-specific process. Time-dependent expression shifts or switches between the arms are also relevant for human diseases. We present miRSwitch, a web server to facilitate the analysis and interpretation of arm selection events. Our species-independent tool evaluates pre-processed small non-coding RNA sequencing (sncRNA-seq) data, i.e. expression matrices or output files from miRNA quantification tools (miRDeep2, miRMaster, sRNAbench). miRSwitch highlights potential changes in the distribution of mature miRNAs from the same precursor. Group comparisons from one or several user-provided annotations (e.g. disease states) are possible. Results can be dynamically adjusted by choosing from a continuous range of highly specific to very sensitive parameters. Users can compare potential arm shifts in the provided data to a human reference map of pre-computed arm shift frequencies. We created this map from 46 tissues and 30,521 samples. As case studies we present novel arm shift information in a Alzheimer’s disease biomarker data set and from a comparison of tissues in Homo sapiens and Mus musculus. In summary, miRSwitch offers a broad range of customised arm switch analyses along with comprehensive visualisations, and is freely available at: https://www.ccb.uni-saarland.de/mirswitch/.


2020 ◽  
Vol 48 (W1) ◽  
pp. W268-W274 ◽  
Author(s):  
Fabian Kern ◽  
Jeremy Amand ◽  
Ilya Senatorov ◽  
Alina Isakova ◽  
Christina Backes ◽  
...  

Abstract Arm selection, the preferential expression of a 3′ or 5′ mature microRNA (miRNA), is a highly dynamic and tissue-specific process. Time-dependent expression shifts or switches between the arms are also relevant for human diseases. We present miRSwitch, a web server to facilitate the analysis and interpretation of arm selection events. Our species-independent tool evaluates pre-processed small non-coding RNA sequencing (sncRNA-seq) data, i.e. expression matrices or output files from miRNA quantification tools (miRDeep2, miRMaster, sRNAbench). miRSwitch highlights potential changes in the distribution of mature miRNAs from the same precursor. Group comparisons from one or several user-provided annotations (e.g. disease states) are possible. Results can be dynamically adjusted by choosing from a continuous range of highly specific to very sensitive parameters. Users can compare potential arm shifts in the provided data to a human reference map of pre-computed arm shift frequencies. We created this map from 46 tissues and 30 521 samples. As case studies we present novel arm shift information in a Alzheimer’s disease biomarker data set and from a comparison of tissues in Homo sapiens and Mus musculus. In summary, miRSwitch offers a broad range of customized arm switch analyses along with comprehensive visualizations, and is freely available at: https://www.ccb.uni-saarland.de/mirswitch/.


Acta Naturae ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 21-33 ◽  
Author(s):  
N. M. Baulina ◽  
O. G. Kulakova ◽  
O. O. Favorova

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level through base-pairing predominantly with a 3-untranslated region of target mRNA, followed by mRNA degradation or translational repression. Totally, miRNAs change, through a complex regulatory network, the expression of more than 60% of human genes. MiRNAs are key regulators of the immune response that affect maturation, proliferation, differentiation, and activation of immune cells, as well as antibody secretion and release of inflammatory mediators. Disruption of this regulation may lead to the development of various pathological conditions, including autoimmune inflammation. This review summarizes the data on biogenesis and the mechanisms of miRNA action. We discuss the role of miRNAs in the development and the action of the immune system, as well as in the development of an autoimmune inflammatory response. Special attention is given to the role of miRNAs in the autoimmune inflammation in multiple sclerosis, which is a serious socially significant disease of the central nervous system. Currently, a lot of research is focused on this problem.


2021 ◽  
Vol 28 ◽  
Author(s):  
Mst Shamima Khatun ◽  
Md Ashad Alam ◽  
Watshara Shoombuatong ◽  
Md Nurul Haque Mollah ◽  
Hiroyuki Kurata ◽  
...  

: MicroRNAs (miRNAs) are central players that regulate the post-transcriptional processes of gene expression. Binding of miRNAs to target mRNAs can repress their translation by inducing the degradation or by inhibiting the translation of the target mRNAs. High-throughput experimental approaches for miRNA target identification are costly and time-consuming, depending on various factors. It is vitally important to develop the bioinformatics methods for accurately predicting miRNA targets. With the increase of RNA sequences in the post-genomic era, bioinformatics methods are being developed for miRNA studies specially for miRNA target prediction. This review summarizes the current development of state-of-the-art bioinformatics tools for miRNA target prediction, points out the progress and limitations of the available miRNA databases, and their working principles. Finally, we discuss the caveat and perspectives of the next-generation algorithms for the prediction of miRNA targets.


2021 ◽  
Author(s):  
Sandali Lokuge ◽  
Shyaman Jayasundara ◽  
Puwasuru Ihalagedara ◽  
Damayanthi Herath ◽  
Indika Kahanda

microRNAs (miRNAs) are known as one of the small non-coding RNA molecules, which control the expressions of genes at the RNA level. They typically range 20-24 nucleotides in length and can be found in the plant and animal kingdoms and in some viruses. Computational approaches have overcome the limitations in the experimental methods and have performed well in identifying miRNAs. Compared to mature miRNAs, precursor miRNAs (pre-miRNAs) are long and have a hairpin loop structure with structural features. Therefore, most in-silico tools are implemented for the pre-miRNAs identification. This study presents a multilayer perceptron (MLP) based classifier implemented using 180 features under sequential, structural, and thermodynamic feature categories for plant pre-miRNA identification. This classifier has a 92% accuracy, 94% specificity, and 90% sensitivity. We have further tested this model with other small non-coding RNA types and obtained 78% accuracy. Furthermore, we introduce a novel dataset to train and test machine learning models, addressing the overlapping data issue in positive training and testing datasets presented in PlantMiRNAPred, a study done by Xuan et al. for the classification of real and pseudo plant pre-miRNAs. The new dataset and the classifier are deployed on a web server which is freely accessible via http://mirnafinder.shyaman.me/.


Author(s):  
Jagriti Chatterjee Subhojyoti Chatterjee,

The functioning of gene expression or ribonucleic acid (RNA) silencing is governed by microRNA also known as miRNA. It is a small non-coding RNA molecule which finds its existence in animals, viruses, or plants. The large part of miRNAs is found to be transcribed from DNA sequences to form primary miRNAs followed by the processing of the precursor miRNAs and mature miRNAs. The miRNAs interconnect with their target genes in an effective manner which is dependent on factors like sub-cellular location of miRNAs, the availability of miRNAs and target miRNAs along with their interaction affinities, as seen in case of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Together with its involvement in normal functioning of eukaryotic cells, microRNA deregulation is associated with cancer, i.e., chronic lymphocytic leukemia. Therefore, microRNA target identification becomes important to unwind the relationship between microRNA deregulation and human diseases, thereby paving a path for structure-baseddrug discovery. Towards that direction, we have attempted to use the platform of PERL programming (a user-friendly and dynamic language to easily process and manipulate long sequences), to detect the microRNA target sites in genomic sequences, thereby trying to suppress the expression level for prognosis.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongwei Yan ◽  
Qi Liu ◽  
Jieming Jiang ◽  
Xufang Shen ◽  
Lei Zhang ◽  
...  

AbstractAlthough sex determination and differentiation are key developmental processes in animals, the involvement of non-coding RNA in the regulation of this process is still not clarified. The tiger pufferfish (Takifugu rubripes) is one of the most economically important marine cultured species in Asia, but analyses of miRNA and long non-coding RNA (lncRNA) at early sex differentiation stages have not been conducted yet. In our study, high-throughput sequencing technology was used to sequence transcriptome libraries from undifferentiated gonads of T. rubripes. In total, 231 (107 conserved, and 124 novel) miRNAs were obtained, while 2774 (523 conserved, and 2251 novel) lncRNAs were identified. Of these, several miRNAs and lncRNAs were predicted to be the regulators of the expression of sex-related genes (including fru-miR-15b/foxl2, novel-167, novel-318, and novel-538/dmrt1, novel-548/amh, lnc_000338, lnc_000690, lnc_000370, XLOC_021951, and XR_965485.1/gsdf). Analysis of differentially expressed miRNAs and lncRNAs showed that three mature miRNAs up-regulated and five mature miRNAs were down-regulated in male gonads compared to female gonads, while 79 lncRNAs were up-regulated and 51 were down-regulated. These findings could highlight a group of interesting miRNAs and lncRNAs for future studies and may reveal new insights into the function of miRNAs and lncRNAs in sex determination and differentiation.


2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Nicolas Cerveau ◽  
Daniel John Jackson

AbstractMicroRNAs (miRNAs) are a deeply conserved class of small, single stranded RNA molecules that post-transcriptionally regulate mRNA levels via several targeted degradation pathways. They are involved in a wide variety of biological processes and have been used to infer the deep evolutionary relationships of major groups such as the Metazoa. Here we have surveyed several adult tissues of the freshwater pulmonate Lymnaea stagnalis (the Great Pond Snail) for miRNAs. In addition we perform a shell regeneration assay to identify miRNAs that may be involved in regulating mRNAs directly involved in the shell-forming process. From seven mature tissues we identify a total of 370 unique precursor miRNAs that give rise to 336 unique mature miRNAs. While the majority of these appear to be evolutionarily novel, most of the 70 most highly expressed (which account for 99.8% of all reads) share sequence similarity with a miRBase or mirGeneDB2.0 entry. We also identify 10 miRNAs that are differentially regulated in mantle tissue that is actively regenerating shell material, 5 of which appear to be evolutionarily novel and none of which share similarity with any miRNA previously reported to regulate biomineralization in molluscs. One significantly down-regulated miRNA is predicted to target Lst-Dermatopontin, a previously characterized shell matrix protein from another freshwater gastropod. This survey provides a foundation for future studies that would seek to characterize the functional role of these molecules in biomineralization or other processes of interest.


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