MiRNAs: Biology, Biogenesis, their Web-based Tools, and Databases

Author(s): Majid Tafrihi*, Elham Hasheminasab.

Journal Name: MicroRNA

Volume 8 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Introduction: MicroRNAs (miRNAs), which are evolutionarily conserved, and endogenous non-coding RNAs, participate in the post-transcriptional regulation of eukaryotic genes. The biogenesis of miRNAs occurs in the nucleus. Then, in the cytoplasm, they are assembled along with some proteins in a ribonucleoprotein complex called RISC. miRNA component of the RISC complex binds to the complementary sequence of mRNA target depending on the degree of complementarity, and leads to mRNA degradation and/or inhibition of protein synthesis. miRNAs have been found in eukaryotes and some viruses play a role in development, metabolism, cell proliferation, growth, differentiation, and death.

Objective: A large number of miRNAs and their targets were identified by different experimental techniques and computational approaches. The principal aim of this paper is to gather information about some miRNA databases and web-based tools for better and quicker access to relevant data.

Results: Accordingly, in this paper, we collected and introduced miRNA databases and some webbased tools that have been developed by various research groups. We have categorized them into different classes including databases for viral miRNAs, and plant miRNAs, miRNAs in human beings, mice and other vertebrates, miRNAs related to human diseases, and target prediction, and miRNA expression. Also, we have presented relevant statistical information about these databases.

Keywords: Biogenesis, databases, miRNA, mRNA target, web-based tools, cytoplasm.

[1]
Grundhoff A, Sullivan CS. Virus-encoded microRNAs. Virology 2011; 411: 325-43.
[2]
Sarnow P, Jopling CL, Norman KL, et al. MicroRNAs: expression, avoidance and subversion by vertebrate viruses. Nat Rev Microbiol 2006; 4: 651-9.
[3]
Melo CA, Melo SA. Biogenesis and physiology of microRNAs.In: non-coding RNAs and cancer; Fabbri M, Ed.; Springer: New York, 2014; pp. 5-24.
[4]
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75: 843-54.
[5]
Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403: 901-6.
[6]
Bartel D. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-97.
[7]
Wahid F, Shehzad A, Khan T, et al. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta 2010; 1803: 1231-43.
[8]
Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell 2009; 136: 642-55.
[9]
Ghorai A, Ghosh U. miRNA gene counts in chromosomes vary widely in a species and biogenesis of miRNA largely depends on transcription or post-transcriptional processing of coding genes. Front Genet 2014; 5: 100.
[10]
Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 2005; 11: 241-7.
[11]
Diederichs S, Haber DA. Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. Cancer Res 2006; 66: 6097-104.
[12]
Yanaihara N, Caplen N, Bowman E, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006; 9: 189-98.
[13]
Kulshreshtha R, Ferracin M, Wojcik SE, et al. A microRNA signature of hypoxia. Mol Cell Biol 2007; 27: 1859-67.
[14]
Pires IM, Bencokova Z, Milani M, et al. Effects of acute versus chronic hypoxia on DNA damage responses and genomic instability. Cancer Res 2010; 70: 925-35.
[15]
Hubbi ME, Luo W, Baek JH, et al. MCM proteins are negative regulators of hypoxia-inducible factor 1. Mol Cell 2011; 42: 700-12.
[16]
Bartel DP. microRNAs: target recognition and regulatory functions. Cell 2009; 136: 215-33.
[17]
Hertel J, Lindemeyer M, Missal K, et al. The expansion of the metazoan microRNA repertoire. BMC Genomics 2006; 7: 25.
[18]
Lee H, Han S, Kwon CS, et al. Biogenesis and regulation of the let-7 miRNAs and their functional implications. Protein Cell 2016; 7: 100-13.
[19]
Ketley A, Warren A, Holms E, et al. The miR-30 microRNA family targets smoothened to regulate hedgehog signalling in zebrafish early muscle development. PLoS One 2013; 8: e65170.
[20]
Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol 2008; 18: 505-16.
[21]
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15: 509-24.
[22]
Monteys AM, Spengler RM, Wan J, et al. Structure and activity of putative intronic miRNA promoters. RNA 2010; 16: 495-505.
[23]
Achkar NA, Cambiagno DA, Manavella PA. miRNA biogenesis: a dynamic pathway. Trends Plant Sci 2016; 21: 1034-44.
[24]
O’Donnell KA, Wentzel EA, Zeller KA, et al. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435: 839-43.
[25]
Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 2006; 13: 1097-101.
[26]
Koo CX, Kobiyama K, Shen YJ, et al. RNA polymerase III regulates cytosolic RNA: DNA hybrids and intracellular microRNA expression. J Biol Chem 2015; 290: 7463-73.
[27]
Van Driessche B, Rodari A, Delacourt N, et al. Characterization of new RNA polymerase III and RNA polymerase II transcriptional promoters in the bovine leukemia virus genome. Sci Rep 2016; 6: 31125.
[28]
Desvignes T, Batzel P, Berezikov E, et al. miRNA nomenclature: a view incorporating genetic origins, biosynthetic pathways, and sequence variants. Trends Genet 2015; 31: 613-26.
[29]
MacFarlane LA, Murphy PR. microRNA: biogenesis, function and role in cancer. Curr Genomics 2010; 11: 537-61.
[30]
Sun W, Julie Li YS, Huang HD, et al. microRNA: a master regulator of cellular processes for bioengineering systems. Annu Rev Biomed Eng 2010; 12: 1-27.
[31]
Zeng C, Xia J, Chen X, et al. MicroRNA-like RNAs from the same miRNA precursors play a role in cassava chilling responses. Sci Rep 2017; 7: 17135.
[32]
Goymer P. Introducing the mirtron. Nat Rev Genet 2007; 8: 568-9.
[33]
Westholm JO, Lai EC. Mirtrons: microRNA biogenesis via splicing. Biochimie 2011; 93: 1897-904.
[34]
Cifuentes D, Xue H, Taylor DW, et al. A novel miRNA processing pathway independent of dicer requires Argonaute2 catalytic activity. Science 2010; 328: 1694-8.
[35]
Yang JS, Maurin T, Robine N, et al. Conserved vertebrate miR-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis. Proc Natl Acad Sci USA 2010; 107: 15163-8.
[36]
Barbiarz JE, Ruby JG, Wang Y, et al. Mouse ES cells express endogenous shRNAs, siRNAs, and other microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 2008; 22: 2773-85.
[37]
Desvignes T, Beam MJ, Batzel P, et al. Expanding the annotation of zebrafish microRNAs based on small RNA sequencing. Gene 2014; 546: 386-9.
[38]
Chen L, Dahlstrom JE, Lee SH, et al. Naturally occurring endo-siRNA silences LINE-1 retrotransposons in human cells through DNA methylation. Epigenetics 2012; 7: 758-71.
[39]
Moran Y, Fredman D, Praher D, et al. Cnidarian microRNAs frequently regulate targets by cleavage. Genome Res 2014; 24: 651-63.
[40]
Stark A, Brennecke J, Bushati N, et al. Animal microRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell 2005; 123: 1133-46.
[41]
Lai EC, Tomancak P, Williams RW, et al. Computational identification of Drosophila microRNA genes. Genome Biol 2003; 4: R42.
[42]
Lewis BP, Shih IH, Jones-Rhoades MW, et al. Prediction of mammalian microRNA targets. Cell 2003; 115: 787-98.
[43]
Stark A, Brennecke J, Russell RB, et al. Identification of Drosophila microRNA targets. PLoS Biol 2003; 1: 397-409.
[44]
Mortensen RD, Serra M, Steitz JA, et al. Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs). Proc Natl Acad Sci USA 2011; 108: 8281-6.
[45]
Truesdell SS, Mortensen RD, Seo M, et al. microRNA-mediated mRNA translation activation in quiescent cells and oocytes involves recruitment of a nuclear microRNP. Sci Rep 2012; 2: 842.
[46]
Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008; 27: 2128-36.
[47]
Forman JJ, Legesse-Miller A, Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci USA 2008; 105: 14879-84.
[48]
Wang WX, Wilfred BR, Xie K, et al. Individual microRNAs (miRNAs) display distinct mRNA targeting “rules”. RNA Biol 2010; 7: 373-80.
[49]
Chen PS, Su JL, Cha ST, et al. miR-107 promotes tumor progression by targeting the let-7 microRNA in mice and humans. J Clin Invest 2011; 121: 3442-55.
[50]
Saxena S, Jónsson ZO, Dutta A. Small RNAs with imperfect match to endogenous mRNA repress translation. J Biol Chem 2003; 278: 44312-9.
[51]
Wienholds E, Plasterk RH. MicroRNA function in animal development. FEBS Lett 2005; 579: 5911-22.
[52]
Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci USA 2007; 104: 9667-72.
[53]
Chen K, Rajewsky N. Natural selection on human microRNA binding sites inferred from SNP data. Nat Genet 2006; 38: 1452-6.
[54]
Chen X. MicroRNA metabolism in plants. Curr Top Microbiol Immunol 2008; 320: 117-36.
[55]
Nottrott S, Simard MJ, Richter JD. Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol 2006; 13: 1108-12.
[56]
Eulalio A, Huntzinger E, Izaurralde E. Getting to the root of miRNA-mediated gene silencing. Cell 2008; 132: 9-14.
[57]
Thermann R, Hentze MW. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature 2007; 447: 875-8.
[58]
Bazzini AA, Lee MT, Giraldez AJ. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science 2012; 336: 233-7.
[59]
Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med 2009; 13: 39-53.
[60]
Calin GA, Cimmino A, Fabbri M, et al. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci USA 2008; 105: 5166-71.
[61]
Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2006; 102: 13944-9.
[62]
Zhang L, Wang T, Wright AF, et al. A microdeletion in Xp11.3 accounts for co-segregation of retinitis pigmentosa and mental retardation in a large kindred. Am J Med Genet A 2006; 140: 349-57.
[63]
Lu M, Zhang Q, Deng M, et al. An analysis of human MicroRNA and disease associations. PLoS One 2008; 3: e3420.
[64]
Mendell JT, Olson EN. MicroRNAs in stress signaling and human disease. Cell 2012; 148(6): 1172-87.
[65]
Das J, Podder S, Ghosh TC. Insights into the miRNA regulations in human disease genes. BMC Genomics 2014; 15: 1010.
[66]
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006; 6: 857-66.
[67]
Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med 2014; 20: 460-9.
[68]
Makunin IV, Pheasant M, Simons C, et al. Orthologous microRNA genes are located in cancer-associated genomic regions in human and mouse. PLoS One 2007; 2: e1133.
[69]
Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101: 2999-3004.
[70]
Zhang X, Cairns M, Rose B, et al. Alterations in miRNA processing and expression in pleomorphic adenomas of the salivary gland. Int J Cancer 2009; 124: 2855-63.
[71]
Li Y, Kowdley KV. MicroRNAs in common human diseases. Genomics Proteomics Bioinformatics 2012; 10: 246-53.
[72]
Liu L, Wang D, Qiu Y, et al. Overexpression of microRNA-15 increases the chemosensitivity of colon cancer cells to 5-flourouracil and Oxaliplatin by inhibiting the nuclear factor-κB signalling pathway and inducing apoptosis. Exp Ther Med 2018; 15: 2655-60.
[73]
Wang B, Hsu SH, Wang X, et al. Reciprocal regulation of miR-122 and c-Myc in hepatocellular cancer: role of E2F1 and TFDP2. Hepatology 2014; 59: 555-66.
[74]
Walz AL, Ooms A, Gadd S, et al. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors. Cancer Cell 2015; 27: 286-97.
[75]
Faggad A, Budczies J, Tchernitsa O, et al. Prognostic significance of Dicer expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression. J Pathol 2010; 220: 382-91.
[76]
Melo SA, Moutinho C, Ropero S, et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell 2010; 18: 303-15.
[77]
Liu S, An J, Lin J, et al. Single nucleotide polymorphisms of microRNA processing machinery genes and outcome of hepatocellular carcinoma. PLoS One 2014; 9: e92791.
[78]
Osuch-Wojcikiewicz E, Bruzgielewicz A, Niemczyk K, et al. Association of polymorphic variants of miRNA processing genes with larynx cancer risk in a polish population. BioMed Res Int 2015; 2015: 298378.
[79]
Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435(7043): 834-8.
[80]
Riaz M, van Jaarsveld MT, Hollestelle A, et al. miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs. Breast Cancer Res 2013; 15: R33.
[81]
Ghazizadeh M, Hadi F, Zare M. Direct Assay of miR-16, miR-145 and miR-223 by a novel method of mimic PCR in serum of breast cancer patients. J Genet Resour 2016; 2: 98-108.
[82]
Thomson DW, Bracken CP, Goodall GJ. Experimental strategies for microRNA target identification. Nucleic Acids Res 2011; 39: 6845-53.
[83]
Liu B, Li J, Cairns MJ. Identifying miRNAs, targets, and functions. Brief Bioinform 2012; 15: 1-19.
[84]
Várallyay E, Burgyán J, Havelda Z. MicroRNA detection by northern blotting using locked nucleic acid probes. Nat Protoc 2008; 3: 190-6.
[85]
Deepak S, Kottapalli K, Rakwal R, et al. Real-time PCR: revolutionizing detection and expression analysis of genes. Curr Genomics 2007; 8: 234-51.
[86]
Varkonyi-Gasic E, Wu R, Wood M, et al. Protocol: a highly sensitive RT-PCR method for detection and quantification of microRNAs. Plant Methods 2007; 3: 12.
[87]
Hunt EA, Broyles D, Head T, et al. MicroRNA detection: current technology and research strategies. Ann Rev Anal Chem 2015; 8: 217-37.
[88]
Li W, Ruan K. MicroRNA detection by microarray. Anal Bioanal Chem 2009; 394: 1117-24.
[89]
Williamson V, Kim A, Xie B, et al. Detecting miRNAs in deep sequencing data: a software performance comparison and evaluation. Brief Bioinform 2012; 14: 36-45.
[90]
Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005; 433: 769-73.
[91]
Hayashida Y, Nishibu T, Inoue K, et al. A useful approach to total analysis of RISC-associated RNA. BMC Res Notes 2009; 2: 169.
[92]
Ørom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 2008; 30: 460-71.
[93]
Andachi Y. A novel biochemical method to identify target genes of individual microRNAs: identification of a new Caenorhabditis elegans let-7 target. RNA 2008; 14: 2440-51.
[94]
Stadler M, Artiles K, Pak J, et al. Contributions of mRNA abundance, ribosome loading, and post- or peri-translational effects to temporal repression of C. elegans heterochronic miRNA targets. Genome Res 2012; 22: 2418-26.
[95]
Guo H, Ingolia NT, Weissman JS, et al. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010; 466: 835-41.
[96]
Zhang X, Zuo X, Yang B, et al. MicroRNA directly enhances mitochondrial translation during muscle differentiation. Cell 2014; 158: 607-19.
[97]
Großhans H, Filipowicz W. Proteomics joins the search for microRNA targets. Cell 2008; 134: 560-2.
[98]
Wu S, Huang S, Ding J, et al. Multiple microRNAs modulate p21Cip1/Waf1 expression by directly targeting its 3′ untranslated region. Oncogene 2010; 29: 2302-8.
[99]
Hashimoto Y, Akiyama Y, Yuasa Y. Multiple-to-multiple relationships between microRNAs and target genes in gastric cancer. PLoS One 2013; 8: e62589.
[100]
Jiang Q, Feng MG, Mo YY. Systematic validation of predicted microRNAs for cyclin D1. BMC Cancer 2009; 9: 194.
[101]
Vo NK, Dalton RP, Liu N, et al. Affinity purification of microRNA-133a with the cardiac transcription factor, Hand2. Proc Natl Acad Sci USA 2010; 107: 19231-6.
[102]
Singh NK. microRNAs databases: developmental methodologies, structural and functional annotations. Interdiscip Sci 2017; 9: 357-77.
[103]
Khurana R, Verma VK, Rawoof A, et al. OncomiRdbB: a comprehensive database of microRNAs and their targets in breast cancer. BMC Bioinformatics 2014; 15: 15.
[104]
Zorc M, Obsteter J, Dovc P, et al. Genetic variability of microRNA genes in 15 animal species. J Genomics 2015; 3: 51-6.
[105]
Gerlach D, Kriventseva EV, Rahman N, et al. miROrtho: computational survey of microRNA genes. Nucleic Acids Res 2009; 37: D111-7.
[106]
Girijadevi R, Sreedevi VC, Sreedharan JV, et al. IntmiR: a complete catalogue of intronic miRNAs of human and mouse. Bioinformation 2011; 5: 458-9.
[107]
Ludwig N, Leidinger P, Becker K, et al. Distribution of miRNA expression across human tissues. Nucleic Acids Res 2016; 44: 3865-77.
[108]
Bhartiya D, Laddha SV, Mukhopadhyay A, et al. miRvar: A comprehensive database for genomic variations in microRNAs. Hum Mutat 2011; 32: E2226-45.
[109]
Mooney C, Becker BA, Raoof R, et al. EpimiRBase: a comprehensive database of microRNA-epilepsy associations. Bioinformatics 2016; 32: 1436-8.
[110]
Laganà A, Paone A, Veneziano D, et al. miR-EdiTar: a database of predicted A-to-I edited miRNA target sites. Bioinformatics 2012; 28: 3166-8.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 8
ISSUE: 1
Year: 2019
Page: [4 - 27]
Pages: 24
DOI: 10.2174/2211536607666180827111633
Price: $58

Article Metrics

PDF: 40
HTML: 4