Integrative approaches for analysis of mRNA and microRNA high-throughput data

Nazarov, Petr V.; Kreis, Stephanie

doi:10.1016/j.csbj.2021.01.029

Cited by 24 publications

(15 citation statements)

References 74 publications

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“…Although miRNA biogenesis pathways have been well characterized, miRNA target identification remains a major challenge. Recent methodological developments in miRNA sequence analysis have significantly improved the accuracy of miRNA target prediction on the genome-wide scale ( Lewis et al 2005 ; Agarwal et al 2015 ; McGeary et al 2019 ; Nazarov and Kreis 2021 ). However, these predictions rely heavily on conserved base-pairing of the miRNA seed region, which can lead to a high error rate given the high frequency of 6-nt seed-matches in the transcriptome ( Pinzon et al 2017 ) and the existence of other functional nonseed interactions between miRNAs and their targets ( Broughton et al 2016 ; Zhang et al 2018 ; Chipman and Pasquinelli 2019 ; McGeary et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

A noncanonical microRNA derived from the snaR-A noncoding RNA targets a metastasis inhibitor

Stribling

Lei

Guardia

et al. 2021

RNA

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MicroRNAs (miRNAs) are small noncoding RNAs that function as critical posttranscriptional regulators in various biological processes. While most miRNAs are generated from processing of long primary transcripts via sequential Drosha and Dicer cleavage, some miRNAs that bypass Drosha cleavage can be transcribed as part of another small noncoding RNA. Here, we develop the target-oriented miRNA discovery (TOMiD) bioinformatic analysis method to identify Drosha-independent miRNAs from Argonaute crosslinking and sequencing of hybrids (Ago-CLASH) data sets. Using this technique, we discovered a novel miRNA derived from a primate specific noncoding RNA, the small NF90 associated RNA A (snaR-A). The miRNA derived from snaR-A (miR-snaR) arises independently of Drosha processing but requires Exportin-5 and Dicer for biogenesis. We identify that miR-snaR is concurrently up-regulated with the full snaR-A transcript in cancer cells. Functionally, miR-snaR associates with Ago proteins and targets NME1, a key metastasis inhibitor, contributing to snaR-A's role in promoting cancer cell migration. Our findings suggest a functional link between a novel miRNA and its precursor noncoding RNA.

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Section: Introductionmentioning

confidence: 99%

A noncanonical microRNA derived from the snaR-A noncoding RNA targets a metastasis inhibitor

Stribling

Lei

Guardia

et al. 2021

RNA

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“…The exploration of miRNAs generally requires the prediction of the seed sequences that bind to the 3′-UTR using various algorithms and de novo or machine learning tools, but various computational analyses could not identify enough binding ability or downstream biological roles of the predicted miRNAs in vitro or in vivo. Accordingly, we selected new potential miRNAs that can bind to the 3′-UTR of HCMV UL123 , which downregulates IE72 expression, using high-throughput sequencing data from AGO-CLIP-seq instead of traditional algorithms in silico, because cellular miRNAs interacting with UL123 -3′-UTR have not been evaluated despite the crucial role of IE72 during early infection [ 13 , 27 , 59 , 63 , 87 , 94 , 95 ]. However, sophisticated SC-based flow cytometry of GFP expression revealed that miRNAs with the most abundant transcripts in AGO-CLIP-seq from HCMV-infected cells did not bind to the 3′-UTR of UL123 .…”

Section: Discussionmentioning

confidence: 99%

Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP

Hong

Min

Kim

et al. 2022

IJMS

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Attenuating the expression of immediate early (IE) proteins is essential for controlling the lytic replication of human cytomegalovirus (HCMV). The human microRNAs (hsa-miRs), miR-200b-3p and miR-200c-3p, have been identified to bind the 3′-untranslated region (3′-UTR) of the mRNA encoding IE proteins. However, whether hsa-miRs can reduce IE72 expression and HCMV viral load or exhibit a crosstalk with the host cellular signaling machinery, most importantly the NF-κB cascade, has not been evaluated. In this study, argonaute-crosslinking and immunoprecipitation-seq revealed that miR-200b-3p and miR-200c-3p bind the 3′-UTR of UL123, which is a gene that encodes IE72. The binding of these miRNAs to the 3′-UTR of UL123 was verified in transfected cells stably expressing GFP. We used miR-200b-3p/miR-200c-3p mimics to counteract the downregulation of these miRNA after acute HCMV infection. This resulted in reduced IE72/IE86 expression and HCMV VL during lytic infection. We determined that IE72/IE86 alone can inhibit the phosphorylation of RelA/p65 at the Ser536 residue and that p-Ser536 RelA/p65 binds to the major IE promoter/enhancer (MIEP). The upregulation of miR-200b-3p and miR-200c-3p resulted in the phosphorylation of RelA/p65 at Ser536 through the downregulation of IE, and the binding of the resultant p-Ser536 RelA/p65 to MIEP resulted in a decreased production of pro-inflammatory cytokines. Overall, miR-200b-3p and miR-200c-3p—together with p-Ser536 RelA/p65—can prevent lytic HCMV replication during acute and latent infection.

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“…It has been long established that miRNAs act cooperatively with other miRNAs and transcription factors that are themselves targeted by miRNAs, typically acting as hubs in regulatory networks. Over the past decade, fed by the increased availability of expression data and high-throughput miRNA target determination, important efforts have been made to develop in silico approaches that integrate this information to identify key regulatory networks ( 211 ). Nevertheless, most available networks are built based on gene-wide miRNA targeting and gene expression correlations, with very little input on regulation of miRNA gene expression.…”

Section: Molecular Mechanisms Underlying Nutrient-mediated Regulation Of Mirna Actionmentioning

confidence: 99%

Molecular Mechanisms of Nutrient-Mediated Regulation of MicroRNAs in Pancreatic β-cells

Salowka

Martínez-Sánchez

2021

Front. Endocrinol.

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Pancreatic β-cells within the islets of Langerhans respond to rising blood glucose levels by secreting insulin that stimulates glucose uptake by peripheral tissues to maintain whole body energy homeostasis. To different extents, failure of β-cell function and/or β-cell loss contribute to the development of Type 1 and Type 2 diabetes. Chronically elevated glycaemia and high circulating free fatty acids, as often seen in obese diabetics, accelerate β-cell failure and the development of the disease. MiRNAs are essential for endocrine development and for mature pancreatic β-cell function and are dysregulated in diabetes. In this review, we summarize the different molecular mechanisms that control miRNA expression and function, including transcription, stability, posttranscriptional modifications, and interaction with RNA binding proteins and other non-coding RNAs. We also discuss which of these mechanisms are responsible for the nutrient-mediated regulation of the activity of β-cell miRNAs and identify some of the more important knowledge gaps in the field.

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Integrative approaches for analysis of mRNA and microRNA high-throughput data

Abstract: Highlights Review on tools and databases linking miRNA and its mRNA targetome. Databases show little overlap in miRNA targetome predictions suggesting strong contextual effects. Deconvolution and deep learning approaches are promising new approaches to improve miRNA targetome predictions.

Cited by 24 publications

References 74 publications

A noncanonical microRNA derived from the snaR-A noncoding RNA targets a metastasis inhibitor

A noncanonical microRNA derived from the snaR-A noncoding RNA targets a metastasis inhibitor

Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP

Molecular Mechanisms of Nutrient-Mediated Regulation of MicroRNAs in Pancreatic β-cells

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