Position Based Nucleotide Analysis of miR168 Family in Higher Plants and its Targets in Mammalian Transcripts

Javed, Mohammed; Solanki, Manish; Sinha, Anshika; Shukla, Lata I.

doi:10.2174/2211536606666170215154151

Cited by 16 publications

(12 citation statements)

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“…The miR168a is part of a conserved family of plant miRNAs among different species, but as we seen in Supplementary Figure 2 and other cited literature (Lang et al, 2019), differences exist between dicot and monocot species. The predicted human targets observed in previously published researches (Zhang et al, 2012; Javed et al, 2017), were not found in the enriched process or sequence similarity with our approaches (see Supplementary Table 1 ). This can have different explanations: (i) four sequence mismatches (two located within the seed region) are present between osa-miR168a and mtr-miR168a, including a G at position 14, recently reported to generate a G:U wobble that limits its binding to LDLRAP1 (Lang et al, 2019); (ii) only 3′ UTR regions were considered in our study, and since osa-miR168a targets the LDLRAP1 CDS region (Zhang et al, 2012), we did not find this match in the target list; (iii) we used the entire length of the miRNA and 100% sequence complementarity instead of only the miRNA seed region (Zhang et al, 2012; Javed et al, 2017).…”

Section: Discussionmentioning

confidence: 45%

“…The relationship between miR168a and AGO1 (ARGONAUTE) has been long studied and experimentally validated in plants (Vaucheret et al, 2006), whereas several other targets of the plant miR168a have been identified and/or validated in humans (Zhang et al, 2012; Javed et al, 2017). Aside being involved in miRNA biogenesis and regulation (Mallory and Vaucheret, 2010), AGO proteins have a myriad of other functions including plant antiviral responses and DNA repair (AGO2) (Harvey et al, 2011; Oliver et al, 2014; Carbonell and Carrington, 2015), miRNA-directed target cleavage (AGO5), and RNA-directed DNA methylation (AGO9) (Oliver et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…Aside being involved in miRNA biogenesis and regulation (Mallory and Vaucheret, 2010), AGO proteins have a myriad of other functions including plant antiviral responses and DNA repair (AGO2) (Harvey et al, 2011; Oliver et al, 2014; Carbonell and Carrington, 2015), miRNA-directed target cleavage (AGO5), and RNA-directed DNA methylation (AGO9) (Oliver et al, 2014). Differently, the validated osa-miR168a target in humans is LDLRAP1, with functions in cholesterol metabolism (Zhang et al, 2012), while other predicted targets included RPL34 (Large Ribosomal Subunit Protein EL34), ATXN1 (Ataxin-1), and ALS2 (Alsin Rho Guanine Nucleotide Exchange Factor) with roles in transcription, ribosome biogenesis, and cell trafficking (Javed et al, 2017). Other genes (ST8SIA1, RGS6, IL18RAP, PVR, SYN2, PPFIA1, ZDHHC18, B3GAT1) were predicted in our network-based pipeline to be targeted by mtr-miR168 in humans ( Supplementary Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

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A Bioinformatics Approach to Explore MicroRNAs as Tools to Bridge Pathways Between Plants and Animals. Is DNA Damage Response (DDR) a Potential Target Process?

et al. 2019

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MicroRNAs, highly-conserved small RNAs, act as key regulators of many biological functions in both plants and animals by post-transcriptionally regulating gene expression through interactions with their target mRNAs. The microRNA research is a dynamic field, in which new and unconventional aspects are emerging alongside well-established roles in development and stress adaptation. A recent hypothesis states that miRNAs can be transferred from one species to another and potentially target genes across distant species. Here, we propose to look into the trans-kingdom potential of miRNAs as a tool to bridge conserved pathways between plant and human cells. To this aim, a novel multi-faceted bioinformatic analysis pipeline was developed, enabling the investigation of common biological processes and genes targeted in plant and human transcriptome by a set of publicly available Medicago truncatula miRNAs. Multiple datasets, including miRNA, gene, transcript and protein sequences, expression profiles and genetic interactions, were used. Three different strategies were employed, namely a network-based pipeline, an alignment-based pipeline, and a M. truncatula network reconstruction approach, to study functional modules and to evaluate gene/protein similarities among miRNA targets. The results were compared in order to find common features, e.g., microRNAs targeting similar processes. Biological processes like exocytosis and response to viruses were common denominators in the investigated species. Since the involvement of miRNAs in the regulation of DNA damage response (DDR)-associated pathways is barely explored, especially in the plant kingdom, a special attention is given to this aspect. Hereby, miRNAs predicted to target genes involved in DNA repair, recombination and replication, chromatin remodeling, cell cycle and cell death were identified in both plants and humans, paving the way for future interdisciplinary advancements.

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Section: Discussionmentioning

confidence: 45%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A Bioinformatics Approach to Explore MicroRNAs as Tools to Bridge Pathways Between Plants and Animals. Is DNA Damage Response (DDR) a Potential Target Process?

et al. 2019

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“…In Solanum tuberosum L (potato), 982 miRNAs have been classified in 71 miRNA families, and as the largest family, miR1128 family have 141 members ( Mian, 2014 ). The specific miRNA can modulate multiple gene targets, for instance, miR168-5p, one variants of the plant miRNA168a, is wide distributed in 28 plants species of 15 plants families and has the potential to regulate 123 genes of human transcriptome ( Javed et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

A Timely Review of Cross-Kingdom Regulation of Plant-Derived MicroRNAs

Yang

et al. 2021

Front. Genet.

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MicroRNAs (miRNAs) belong to a class of non-coding RNAs that suppress gene expression by complementary oligonucleotide binding to the sites in target messenger RNAs. Numerous studies have demonstrated that miRNAs play crucial role in virtually all cellular processes of both plants and animals, such as cell growth, cell division, differentiation, proliferation and apoptosis. The study of rice MIR168a has demonstrated for the first time that exogenous plant MIR168a influences cholesterol transport in mice by inhibiting low-density lipoprotein receptor adapter protein 1 expression. Inspired by this finding, the cross-kingdom regulation of plant-derived miRNAs has drawn a lot of attention because of its capability to provide novel therapeutic agents in the treatment of miRNA deregulation-related diseases. Notably, unlike mRNA, some plant miRNAs are robust because of their 3′ end modification, high G, C content, and the protection by microvesicles, miRNAs protein cofactors or plant ingredients. The stability of these small molecules guarantees the reliability of plant miRNAs in clinical application. Although the function of endogenous miRNAs has been widely investigated, the cross-kingdom regulation of plant-derived miRNAs is still in its infancy. Herein, this review summarizes the current knowledge regarding the anti-virus, anti-tumor, anti-inflammatory, anti-apoptosis, immune modulation, and intestinal function regulation effects of plant-derived miRNAs in mammals. It is expected that exploring the versatile role of plant-derived miRNAs may lay the foundation for further study and application of these newly recognized, non-toxic, and inexpensive plant active ingredients.

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“…Some studies have found minor concentrations of pl-miR in humans and animals (Zhang et al, 2016). The inclusion of pl-miR into the recipient’s organism causes reproducible changes of some properties and physiological processes in it (Cui et al, 2017; Javed et al, 2017; Lang et al, 2019; Vaucheret et al, 2012; Zhang et al, 2012). ex-miR involvement in the regulation of recipient gene expression may affect disease (Chin, Fong & Somlo, 2016; Gopinath, 2019; Hou et al, 2018; Jones et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Human Genes AreIn SilicoPotential Targets For Rice miRNA

Rakhmetullina

Pyrkova

Aisina

et al. 2020

Preprint

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16Exogenous miRNAs enter the human body through food, and their effects on metabolic 17 processes can be considerable. It is important to determine which miRNAs from plants 18 affect the expression of human genes and the extent of their influence. The binding sites of 19 738 osa-miRNAs that interact with 17508 mRNAs of human genes were determined using 20 the MirTarget program. The characteristics of the binding of 46 single osa-miRNAs to 86 21 mRNAs of human genes with a value of free energy (ΔG) interaction equal 94% to 100% 22 from maximum ΔG were established. The findings showed that osa-miR2102-5p, osa-23 miR5075-3p, osa-miR2097-5p, osa-miR2919 targeted the largest number of genes at 38, 36, 24 23, 19 sites, respectively. mRNAs of 86 human genes were identified as targets for 93 osa-25 miRNAs of all family osa-miRNAs with ΔG values equal 94% to 98% from maximum ΔG. 26Each miRNA of the osa-miR156-5p, osa-miR164-5p, osa-miR168-5p, osa-miR395-3p, osa-27 miR396-3p, osa-miR396-5p, osa-miR444-3p, osa-miR529-3p, osa-miR1846-3p, osa-28 miR2907-3p families had binding sites in mRNAs of several human target genes. The 29 binding sites of osa-miRNAs in mRNAs of the target genes for each family of osa-miRNAs 30 were conserved when compared to flanking nucleotide sequences. mRNA human genes of 31 osa-miRNAs are candidate genes of cancer, cardiovascular and neurodegenerative diseases.32 33 104genes. Each of the 35 miRNAs could bind to mRNAs of one target gene, six miRNAs had targets 105 with two genes, and four miRNAs had three target genes with a value ΔG/ΔGm equal to 94-106 98%. miR2102-5p had 11 target genes with a value ΔG/ΔGm of 94-100%, and the free energy of 107 the interaction of the miRNAs with the mRNAs of these genes varied from -115 kJ/mole to -121 108 4 kJ/mole. The miR2102-5p binding sites were located mainly in the 5'UTR, which suggests that 109 they have a role in the early inhibition of the translation process. However, this property of 110 miR2102-5p indicates the need to control its plant food-derived concentration in the human 111 body. 19 target genes were associated with miR2919. miR5075-3p could bind to three mRNAs at 112 binding sites located in the coding domain sequence and the 5'-untranslated region. The high-113 affinity binding sites were located in the 5'UTR and CDS of the mRNAs with the ΔG/ΔGm value 114 was 94-98%. 17 miRNA binding sites were located in 5'UTR, 39 in CDS and 33 in 3'-115 untranslated region. Therefore, monitoring the concentrations of miR2102-5p, miR2919 and 116 miR5075-3p in human biological fluids is also necessary. 117 118 122 development of cancer of various types: ENAH, MAPT, PRKCE, PRRT2, RBMS2, RHOBTB2, 123 RPS6KA5 and ZFHX3 -breast cancer (Aisina et al., 2019); ADAMTS5, PRAPRGG1A, PVR, 124 SPRY4 -colorectal cancer; CHSY1 -colorectal cancer and hepatocellular carcinoma; PPM1F, 125 FXYD6, DUT, FAM83H -hepatocellular carcinoma; HK2 -gallbladder cancer and leukaemia; 126 C19orf6 -ovarian carcinoma; AFAP1 -oesophageal adenocarcinoma; IOGAP1 -pancreatic 127 6 ductal adenoca...

show abstract

Position Based Nucleotide Analysis of miR168 Family in Higher Plants and its Targets in Mammalian Transcripts

Abstract: Our work suggests that miR168 family has conserved sequence in higher plants. The seed region position 2-8 shows 70-95% pairing with human targets. Cleavage site at position 10-14 and these were analysed for the base preference with the targets showed 80-96% Watson Crick pairing.

Cited by 16 publications

References 0 publications

A Bioinformatics Approach to Explore MicroRNAs as Tools to Bridge Pathways Between Plants and Animals. Is DNA Damage Response (DDR) a Potential Target Process?

A Bioinformatics Approach to Explore MicroRNAs as Tools to Bridge Pathways Between Plants and Animals. Is DNA Damage Response (DDR) a Potential Target Process?

A Timely Review of Cross-Kingdom Regulation of Plant-Derived MicroRNAs

Human Genes AreIn SilicoPotential Targets For Rice miRNA

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