Computational prediction of novel human miRNAs/miRNA target sites in correlation with SNP (rs678653) at 3’UTR of cyclin D1 gene

MicroRNAs (miRNAs) and their target genes play vital roles in crops. However, the genetic variations in miRNA-targeted sites that affect miRNA cleavage efficiency and their correlations with agronomic traits in crops remain unexplored. On the basis of a genome-wide DNA re-sequencing of 210 elite rapeseed (Brassica napus) accessions, we identified the single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs) in miRNA-targeted sites complementary to miRNAs. Variant calling revealed 7.14 million SNPs and 2.89 million INDELs throughout the genomes of 210 rapeseed accessions. Furthermore, we detected 330 SNPs and 79 INDELs in 357 miRNA target sites, of which 33.50% were rare variants. We also analyzed the correlation between the genetic variations in miRNA target sites and 12 rapeseed agronomic traits. Eleven SNPs in miRNA target sites were significantly correlated with phenotypes in three consecutive years. More specifically, three correlated SNPs within the miRNA-binding regions of BnSPL9-3, BnSPL13-2, and BnCUC1-2 were in the loci associated with the branch angle, seed weight, and silique number, respectively; expression profiling suggested that the variation at these 3 miRNA target sites significantly affected the expression level of the corresponding target genes. Taken together, the results of this study provide researchers and breeders with a global view of the genetic variations in miRNA-targeted sites in rapeseed and reveal the potential effects of these genetic variations on elite agronomic traits.

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Comprehensive Overview and Assessment of microRNA Target Prediction Tools in Homo sapiens and Drosophila melanogaster

Current Bioinformatics ◽

10.2174/1574893614666190103101033 ◽

2019 ◽

Vol 14 (5) ◽

pp. 432-445 ◽

Cited By ~ 3

Author(s):

Muniba Faiza ◽

Khushnuma Tanveer ◽

Saman Fatihi ◽

Yonghua Wang ◽

Khalid Raza

Keyword(s):

Drosophila Melanogaster ◽

Mirna Target ◽

Homo Sapiens ◽

Target Prediction ◽

Computational Prediction ◽

Transcriptional Level ◽

Mirna Target Prediction ◽

Microrna Target ◽

Prediction Tools ◽

Mirna Targets

Background: MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression at the post-transcriptional level through complementary base pairing with the target mRNA, leading to mRNA degradation and blocking translation process. Many dysfunctions of these small regulatory molecules have been linked to the development and progression of several diseases. Therefore, it is necessary to reliably predict potential miRNA targets. Objective: A large number of computational prediction tools have been developed which provide a faster way to find putative miRNA targets, but at the same time, their results are often inconsistent. Hence, finding a reliable, functional miRNA target is still a challenging task. Also, each tool is equipped with different algorithms, and it is difficult for the biologists to know which tool is the best choice for their study. Methods: We analyzed eleven miRNA target predictors on Drosophila melanogaster and Homo sapiens by applying significant empirical methods to evaluate and assess their accuracy and performance using experimentally validated high confident mature miRNAs and their targets. In addition, this paper also describes miRNA target prediction algorithms, and discusses common features of frequently used target prediction tools. Results: The results show that MicroT, microRNA and CoMir are the best performing tool on Drosopihla melanogaster; while TargetScan and miRmap perform well for Homo sapiens. The predicted results of each tool were combined in order to improve the performance in both the datasets, but any significant improvement is not observed in terms of true positives. Conclusion: The currently available miRNA target prediction tools greatly suffer from a large number of false positives. Therefore, computational prediction of significant targets with high statistical confidence is still an open challenge.

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Bioinformatics Methods for Studying MicroRNA and ARE-Mediated Regulation of Post-Transcriptional Gene Expression

International Journal of Knowledge Discovery in Bioinformatics ◽

10.4018/jkdb.2010070106 ◽

2010 ◽

Vol 1 (3) ◽

pp. 97-112 ◽

Cited By ~ 3

Author(s):

Richipal Singh Bindra ◽

Jason T. L. Wang ◽

Paramjeet Singh Bagga

Keyword(s):

Mirna Target ◽

Target Prediction ◽

Untranslated Regions ◽

Regulatory Rna ◽

Rna Motifs ◽

Protein Coding ◽

Rna Molecules ◽

Cellular Processes ◽

Target Sites ◽

Transcriptional Gene Regulation

MicroRNAs (miRNAs) are short single-stranded RNA molecules with 21-22 nucleotides known to regulate post-transcriptional expression of protein-coding genes involved in most of the cellular processes. Prediction of miRNA targets is a challenging bioinformatics problem. AU-rich elements (AREs) are regulatory RNA motifs found in the 3’ untranslated regions (UTRs) of mRNAs, and they play dominant roles in the regulated decay of short-lived human mRNAs via specific interactions with proteins. In this paper, the authors review several miRNA target prediction tools and data sources, as well as computational methods used for the prediction of AREs. The authors discuss the connection between miRNA and ARE-mediated post-transcriptional gene regulation. Finally, a data mining method for identifying the co-occurrences of miRNA target sites in ARE containing genes is presented.

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An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations

International Journal of Genomics ◽

10.1155/2017/1674827 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Xianyue Wang ◽

Hong Jiang ◽

Wei Wu ◽

Rongxin Zhang ◽

Lingxiang Wu ◽

...

Keyword(s):

Drug Targets ◽

Large Scale ◽

Drug Response ◽

Mirna Target ◽

Mrna Translation ◽

Gene Interaction ◽

Mirna Regulation ◽

Small Noncoding Rnas ◽

Target Sites ◽

Drug Efficiency

MicroRNAs (miRNAs) are a class of evolutionarily conserved small noncoding RNAs, ~22 nt in length, and found in diverse organisms and play important roles in the regulation of mRNA translation and degradation. It was shown that miRNAs were involved in many key biological processes through regulating the expression of targets. Genetic polymorphisms in miRNA target sites may alter miRNA regulation and therefore result in the alterations of the drug targets. Recent studies have demonstrated that SNPs in miRNA target sites can affect drug efficiency. However, there are still a large number of specific genetic variants related to drug efficiency that are yet to be discovered. We integrated large scale of genetic variations, drug targets, gene interaction networks, biological pathways, and seeds region of miRNA to identify miRNA polymorphisms affecting drug response. In addition, harnessing the abundant high quality biological network/pathways, we evaluated the cascade distribution of tarSNP impacts. We showed that the predictions can uncover most of the known experimentally supported cases as well as provide informative candidates complementary to existing methods/tools. Although there are several existing databases predicting the gain or loss of targeting function of miRNA mediated by SNPs, such as PolymiRTS, miRNASNP, MicroSNiPer, and MirSNP, none of them evaluated the influences of tarSNPs on drug response alterations. We developed a user-friendly online database of this approach named Mir2Drug.

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Identification and Validation of miRNA Target Sites Within Nontraditional miRNA Targets

Methods in Molecular Biology - Regulatory Non-Coding RNAs ◽

10.1007/978-1-4939-1369-5_5 ◽

2014 ◽

pp. 53-67 ◽

Cited By ~ 2

Author(s):

Scott T. Younger ◽

David R. Corey

Keyword(s):

Mirna Target ◽

Mirna Targets ◽

Target Sites

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The microRNA target site landscape is a novel molecular feature associating alternative polyadenylation with immune evasion activity in breast cancer

Briefings in Bioinformatics ◽

10.1093/bib/bbaa191 ◽

2020 ◽

Author(s):

Soyeon Kim ◽

YuLong Bai ◽

Zhenjiang Fan ◽

Brenda Diergaarde ◽

George C Tseng ◽

...

Keyword(s):

Breast Cancer ◽

Mirna Target ◽

Alternative Polyadenylation ◽

Regulatory Elements ◽

Target Site ◽

Mirna Target Site ◽

Breast Cancer Data ◽

Microrna Target ◽

Cancer Data ◽

Target Sites

Abstract Alternative polyadenylation (APA) in breast tumor samples results in the removal/addition of cis-regulatory elements such as microRNA (miRNA) target sites in the 3′-untranslated region (3′-UTRs) of genes. Although previous computational APA studies focused on a subset of genes strongly affected by APA (APA genes), we identify miRNAs of which widespread APA events collectively increase or decrease the number of target sites [probabilistic inference of microRNA target site modification through APA (PRIMATA-APA)]. Using PRIMATA-APA on the cancer genome atlas (TCGA) breast cancer data, we found that the global APA events change the number of the target sites of particular microRNAs [target sites modified miRNA (tamoMiRNA)] enriched for cancer development and treatments. We also found that when knockdown (KD) of NUDT21 in HeLa cells induces a different set of widespread 3′-UTR shortening than TCGA breast cancer data, it changes the target sites of the common tamoMiRNAs. Since the NUDT21 KD experiment previously demonstrated the tumorigenic role of APA events in a miRNA dependent fashion, this result suggests that the APA-initiated tumorigenesis is attributable to the miRNA target site changes, not the APA events themselves. Further, we found that the miRNA target site changes identify tumor cell proliferation and immune cell infiltration to the tumor microenvironment better than the miRNA expression levels or the APA events themselves. Altogether, our computational analyses provide a proof-of-concept demonstration that the miRNA target site information indicates the effect of global APA events with a potential as predictive biomarker.

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SARS-CoV-2 may regulate cellular responses through depletion of specific host miRNAs

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00252.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. L444-L455 ◽

Cited By ~ 5

Author(s):

Rafal Bartoszewski ◽

Michal Dabrowski ◽

Bogdan Jakiela ◽

Sadis Matalon ◽

Kevin S. Harrod ◽

...

Keyword(s):

Immune Responses ◽

Mirna Target ◽

Cellular Responses ◽

Specific Host ◽

Global Pandemic ◽

Target Sites ◽

Bioinformatic Approaches ◽

Mirna Sponges ◽

Human Coronaviruses ◽

Respiratory Coronavirus

Cold viruses have generally been considered fairly innocuous until the appearance of the severe acute respiratory coronavirus 2 (SARS-CoV-2) in 2019, which caused the coronavirus disease 2019 (COVID-19) global pandemic. Two previous viruses foreshadowed that a coronavirus could potentially have devastating consequences in 2002 [severe acute respiratory coronavirus (SARS-CoV)] and in 2012 [Middle East respiratory syndrome coronavirus (MERS-CoV)]. The question that arises is why these viruses are so different from the relatively harmless cold viruses. On the basis of an analysis of the current literature and using bioinformatic approaches, we examined the potential human miRNA interactions with the SARS-CoV-2’s genome and compared the miRNA target sites in seven coronavirus genomes that include SARS-CoV-2, MERS-CoV, SARS-CoV, and four nonpathogenic coronaviruses. Here, we discuss the possibility that pathogenic human coronaviruses, including SARS-CoV-2, could modulate host miRNA levels by acting as miRNA sponges to facilitate viral replication and/or to avoid immune responses.

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