MicroRNAs (miRNAs) are a unique class of short endogenous RNAs, which have become known in the past few decades as major players in gene regulation at the post-transcriptional level. Their regulatory roles make miRNAs crucial for normal development and physiology in several distinct groups of eukaryotes including plants and animals. The common notion is that miRNAs have evolved independently in those distinct lineages, but recent evidence from non-bilaterian metazoans, plants, and various algae raise the possibility that the last common ancestor of these lineages might already have employed an miRNA pathway for post-transcriptional regulation. In this Review we present the commonalities and differences of the miRNA pathways in various eukaryotes and discuss the contrasting scenarios of their possible evolutionary origin and their proposed link to organismal complexity and multicellularity.
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Ameres, S. L. & Zamore, P. D. Diversifying microRNA sequence and function. Nat. Rev. Mol. Cell Biol. 14, 475–488 (2013).
Voinnet, O. Origin, biogenesis, and activity of plant microRNAs. Cell 136, 669–687 (2009).
Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).
Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009).
Reinhart, B. J., Weinstein, E. G., Rhoades, M. W., Bartel, B. & Bartel, D. P. MicroRNAs in plants. Genes Dev. 16, 1616–1626 (2002).
Iwasaki, Y. W., Siomi, M. C. & Siomi, H. PIWI-interacting RNA: its biogenesis and functions. Annu. Rev. Biochem. 84, 405–433 (2015).
Kim, V. N., Han, J. & Siomi, M. C. Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell Biol. 10, 126–139 (2009).
Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 (1993).
Wightman, B., Ha, I. & Ruvkun, G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855–862 (1993).
Giraldez, A. J. et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science 308, 833–838 (2005).
Chen, X. Small RNAs and their roles in plant development. Annu. Rev. Cell Dev. 25, 21–44 (2009).
Peterson, K. J., Dietrich, M. R. & McPeek, M. A. MicroRNAs and metazoan macroevolution: insights into canalization, complexity, and the Cambrian explosion. Bioessays 31, 736–747 (2009).
Grimson, A. et al. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455, 1193–1197 (2008).
Tarver, J. E. et al. microRNAs and the evolution of complex multicellularity: identification of a large, diverse complement of microRNAs in the brown alga Ectocarpus. Nucleic Acids Res. 43, 6384–6398 (2015).
Erwin, D. H. et al. The Cambrian conundrum: early divergence and later ecological success in the early history of animals. Science 334, 1091–1097 (2011).
Axtell, M. J., Westholm, J. O. & Lai, E. C. Vive la différence: biogenesis and evolution of microRNAs in plants and animals. Genome Biol. 12, 221 (2011).
Robinson, J. M. et al. The identification of microRNAs in calcisponges: independent evolution of microRNAs in basal metazoans. J. Exp. Zool. B 320, 84–93 (2013).
Maxwell, E. K., Ryan, J. F., Schnitzler, C. E., Browne, W. E. & Baxevanis, A. D. MicroRNAs and essential components of the microRNA processing machinery are not encoded in the genome of the ctenophore Mnemiopsis leidyi. BMC Genomics 13, 714 (2012).
Ryan, J. F. et al. The genome of the ctenophore Mnemiopsis leidyi and its implications for cell type evolution. Science 342, 1242592 (2013).
Moroz, L. L. et al. The ctenophore genome and the evolutionary origins of neural systems. Nature 510, 109–114 (2014).
Tarver, J. E., Donoghue, P. C. & Peterson, K. J. Do miRNAs have a deep evolutionary history? Bioessays 34, 857–866 (2012).
Molnár, A., Schwach, F., Studholme, D. J., Thuenemann, E. C. & Baulcombe, D. C. miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii. Nature 447, 1126–1129 (2007).
Alaba, S. et al. The liverwort Pellia endiviifolia shares microtranscriptomic traits that are common to green algae and land plants. New Phytol. 206, 352–367 (2015).
Fromm, B. et al. A uniform system for the annotation of human microRNA genes and the evolution of the human microRNAome. Annu. Rev. Genet. 49, 213–242 (2015).
Cerutti, H. & Casas-Mollano, J. A. On the origin and functions of RNA-mediated silencing: from protists to man. Curr. Genet. 50, 81–99 (2006).
Millar, A. A. & Waterhouse, P. M. Plant and animal microRNAs: similarities and differences. Funct. Integr. Genomics 5, 129–135 (2005).
Ghildiyal, M. & Zamore, P. D. Small silencing RNAs: an expanding universe. Nat. Rev. Genet. 10, 94–108 (2009).
Jones-Rhoades, M. W., Bartel, D. P. & Bartel, B. MicroRNAs and their regulatory roles in plants. Annu. Rev. Plant Biol. 57, 19–53 (2006).
Zhao, T. et al. A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. Genes Dev. 21, 1190–1203 (2007).
Avesson, L., Reimegård, J., Wagner, E. G. H. & Söderbom, F. MicroRNAs in Amoebozoa: deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs. RNA 18, 1771–1782 (2012).
Hinas, A. et al. The small RNA repertoire of Dictyostelium discoideum and its regulation by components of the RNAi pathway. Nucleic Acids Res. 35, 6714–6726 (2007).
Huang, P.-J. et al. Identification of putative miRNAs from the deep-branching unicellular flagellates. Genomics 99, 101–107 (2012).
Cuperus, J. T., Fahlgren, N. & Carrington, J. C. Evolution and functional diversification of MIRNA genes. Plant Cell 23, 431–442 (2011).
Fahlgren, N. et al. MicroRNA gene evolution in Arabidopsis lyrata and Arabidopsis thaliana. Plant Cell 22, 1074–1089 (2010).
Axtell, M. J., Snyder, J. A. & Bartel, D. P. Common functions for diverse small RNAs of land plants. Plant Cell 19, 1750–1769 (2007).
Li, J., Wu, Y. & Qi, Y. MicroRNAs in a multicellular green alga Volvox carteri. Sci. China Life Sci. 57, 36–45 (2014).
Herron, M. D., Hackett, J. D., Aylward, F. O. & Michod, R. E. Triassic origin and early radiation of multicellular volvocine algae. Proc. Natl Acad. Sci. USA 106, 3254–3258 (2009).
Thomson, R. C., Plachetzki, D. C., Mahler, D. L. & Moore, B. R. A critical appraisal of the use of microRNA data in phylogenetics. Proc. Natl Acad. Sci. USA 111, E3659–E3668 (2014).
Fromm, B., Worren, M. M., Hahn, C., Hovig, E. & Bachmann, L. Substantial loss of conserved and gain of novel microRNA families in flatworms. Mol. Biol. Evol. 30, 2619–2628 (2013).
Lu, J. et al. The birth and death of microRNA genes in Drosophila. Nat. Genet. 40, 351–355 (2008).
Berezikov, E. et al. Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Nature Genet. 42, 6–9 (2010).
Shaw, W. R., Armisen, J., Lehrbach, N. J. & Miska, E. A. The conserved miR-51 microRNA family is redundantly required for embryonic development and pharynx attachment in Caenorhabditis elegans. Genetics 185, 897–905 (2010).
Chen, K. & Rajewsky, N. The evolution of gene regulation by transcription factors and microRNAs. Nat. Rev. Genet. 8, 93–103 (2007).
Krishna, S. et al. Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata. Nucleic Acids Res. 41, 599–616 (2013).
Moran, Y. et al. Cnidarian microRNAs frequently regulate targets by cleavage. Genome Res. 24, 651–663 (2014).
Arazi, T. et al. Cloning and characterization of micro-RNAs from moss. Plant J. 43, 837–848 (2005).
Schwab, R. et al. Specific effects of microRNAs on the plant transcriptome. Dev. Cell 8, 517–527 (2005).
Lin, S. et al. The Symbiodinium kawagutii genome illuminates dinoflagellate gene expression and coral symbiosis. Science 350, 691–694 (2015).
Saraiya, A. A. & Wang, C. C. snoRNA, a novel precursor of microRNA in Giardia lamblia. PLoS Pathog. 4, e1000224 (2008).
de Jong, D. et al. Multiple dicer genes in the early-diverging metazoa. Mol. Biol. Evol. 26, 1333–1340 (2009).
Ding, S.-W. RNA-based antiviral immunity. Nat. Rev. Immunol. 10, 632–644 (2010).
Kwon, S. C. et al. Structure of Human DROSHA. Cell 164, 81–90 (2016).
Valli, A. A. et al. Most microRNAs in the single-cell alga Chlamydomonas reinhardtii are produced by Dicer-like 3-mediated cleavage of introns and untranslated regions of coding RNAs. Genome Res. 26, 519–529 (2016).
Moran, Y., Praher, D., Fredman, D. & Technau, U. The evolution of microRNA pathway protein components in Cnidaria. Mol. Biol. Evol. 30, 2541–2552 (2013).
Burger, K. & Gullerova, M. Swiss army knives: non-canonical functions of nuclear Drosha and Dicer. Nat. Rev. Mol. Cell Biol. (2015).
Vazquez, F., Gasciolli, V., Crété, P. & Vaucheret, H. The nuclear dsRNA binding protein HYL1 is required for microRNA accumulation and plant development, but not posttranscriptional transgene silencing. Curr. Biol. 14, 346–351 (2004).
Han, M.-H., Goud, S., Song, L. & Fedoroff, N. The Arabidopsis double-stranded RNA-binding protein HYL1 plays a role in microRNA-mediated gene regulation. Proc. Natl Acad. Sci. USA 101, 1093–1098 (2004).
Sabin, L. R. et al. Ars2 regulates both miRNA-and siRNA-dependent silencing and suppresses RNA virus infection in Drosophila. Cell 138, 340–351 (2009).
Lee, Y. et al. The role of PACT in the RNA silencing pathway. EMBO J. 25, 522–532 (2006).
Forstemann, K. et al. Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol. 3, 1187 (2005).
Chendrimada, T. P. et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436, 740–744 (2005).
Allen, E. et al. Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana. Nat. Genet. 36, 1282–1290 (2004).
Kim, V. N. & Nam, J.-W. Genomics of microRNA. Trends Genet. 22, 165–173 (2006).
Merchan, F., Boualem, A., Crespi, M. & Frugier, F. Plant polycistronic precursors containing non-homologous microRNAs target transcripts encoding functionally related proteins. Genome Biol. 10, R136 (2009).
Rodriguez, A., Griffiths-Jones, S., Ashurst, J. L. & Bradley, A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 14, 1902–1910 (2004).
Rajagopalan, R., Vaucheret, H., Trejo, J. & Bartel, D. P. A diverse and evolutionarily fluid set of microRNAs in Arabidopsis thaliana. Genes Dev. 20, 3407–3425 (2006).
Zhu, Q.-H. et al. A diverse set of microRNAs and microRNA-like small RNAs in developing rice grains. Genome Res. 18, 1456–1465 (2008).
Joshi, P. K. et al. Identification of mirtrons in rice using MirtronPred: a tool for predicting plant mirtrons. Genomics 99, 370–375 (2012).
Ameres, S. L. et al. Target RNA–directed trimming and tailing of small silencing RNAs. Science 328, 1534–1539 (2010).
Yu, B. et al. Methylation as a crucial step in plant microRNA biogenesis. Science 307, 932–935 (2005).
Swarts, D. C. et al. The evolutionary journey of Argonaute proteins. Nat. Struct. Mol. Biol. 21, 743–753 (2014).
Ryan, J. F. & Chiodin, M. Where is my mind? How sponges and placozoans may have lost neural cell types. Phil. Trans. R. Soc. B 370, 20150059 (2015).
Drinnenberg, I. A., Fink, G. R. & Bartel, D. P. Compatibility with killer explains the rise of RNAi-deficient fungi. Science 333, 1592–1592 (2011).
Hutvagner, G. & Simard, M. J. Argonaute proteins: key players in RNA silencing. Nat. Rev. Mol. Cell Biol. 9, 22–32 (2008).
Meister, G. Argonaute proteins: functional insights and emerging roles. Nat Rev. Genet. 14, 447–459 (2013).
Okamura, K., Ishizuka, A., Siomi, H. & Siomi, M. C. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev. 18, 1655–1666 (2004).
Swarts, D. C. et al. DNA-guided DNA interference by a prokaryotic Argonaute. Nature 507, 258–261 (2014).
Song, J.-J., Smith, S. K., Hannon, G. J. & Joshua-Tor, L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305, 1434–1437 (2004).
Wang, Y. et al. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 456, 921–926 (2008).
Olovnikov, I., Chan, K., Sachidanandam, R., Newman, D. K. & Aravin, A. A. Bacterial argonaute samples the transcriptome to identify foreign DNA. Mol. Cell 51, 594-605 (2013).
Carthew, R. W. & Sontheimer, E. J. Origins and mechanisms of miRNAs and siRNAs. Cell 136, 642–655 (2009).
Rhoades, M. W. et al. Prediction of plant microRNA targets. Cell 110, 513–520 (2002).
Iwakawa, H.-o . & Tomari, Y. Molecular insights into microRNA-mediated translational repression in plants. Mol. Cell 52, 591–601 (2013).
Liu, Q., Wang, F. & Axtell, M. J. Analysis of complementarity requirements for plant microRNA targeting using a Nicotiana benthamiana quantitative transient assay. Plant Cell 26, 741–753 (2014).
Burki, F., Okamoto, N., Pombert, J.-F. & Keeling, P. J. The evolutionary history of haptophytes and cryptophytes: phylogenomic evidence for separate origins. Proc. R. Soc. Lon. B 279, 2255–2261 (2012).
Philippe, H. et al. Resolving difficult phylogenetic questions: why more sequences are not enough. PLoS Biol. 9, e1000602 (2011).
Selbach, M. et al. Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58–63 (2008).
Baek, D. et al. The impact of microRNAs on protein output. Nature 455, 64–71 (2008).
Muddashetty, R. S. et al. Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Mol. Cell 42, 673–688 (2011).
Bhattacharyya, S. N., Habermacher, R., Martine, U., Closs, E. I. & Filipowicz, W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125, 1111–1124 (2006).
Fabian, M. R. & Sonenberg, N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat. Struct. Mol. Biol. 19, 586–593 (2012).
Huntzinger, E. & Izaurralde, E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat. Rev. Genet. 12, 99–110 (2011).
Chekulaeva, M. et al. miRNA repression involves GW182-mediated recruitment of CCR4–NOT through conserved W-containing motifs. Nat. Struct. Mol. Biol. 18, 1218–1226 (2011).
Meister, G. et al. Identification of novel argonaute-associated proteins. Curr. Biol. 15, 2149–2155 (2005).
Kuzuoğlu-Öztürk, D., Huntzinger, E., Schmidt, S. & Izaurralde, E. The Caenorhabditis elegans GW182 protein AIN-1 interacts with PAB-1 and subunits of the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Nucleic Acids Res. 40, 5651–5665 (2012).
Hutvágner, G. & Zamore, P. D. A microRNA in a multiple-turnover RNAi enzyme complex. Science 297, 2056–2060 (2002).
Brodersen, P. et al. Widespread translational inhibition by plant miRNAs and siRNAs. Science 320, 1185–1190 (2008).
Reis, R. S., Hart-Smith, G., Eamens, A. L., Wilkins, M. R. & Waterhouse, P. M. Gene regulation by translational inhibition is determined by Dicer partnering proteins. Nat. Plants 1, 14027 (2015).
Yang, L., Wu, G. & Poethig, R. S. Mutations in the GW-repeat protein SUO reveal a developmental function for microRNA-mediated translational repression in Arabidopsis. Proc. Natl Acad. Sci. USA 109, 315–320 (2012).
Karginov, F. V. et al. Diverse endonucleolytic cleavage sites in the mammalian transcriptome depend upon microRNAs, Drosha, and additional nucleases. Mol. Cell 38, 781–788 (2010).
Shin, C. et al. Expanding the microRNA targeting code: functional sites with centered pairing. Mol. Cell 38, 789–802 (2010).
Faehnle, C. R., Elkayam, E., Haase, A. D., Hannon, G. J. & Joshua-Tor, L. The making of a slicer: activation of human Argonaute-1. Cell Rep. 3, 1901–1909 (2013).
Hauptmann, J. et al. Turning catalytically inactive human Argonaute proteins into active slicer enzymes. Nat. Struct. Mol. Biol. 20, 814–817 (2013).
Cheloufi, S., Dos Santos, C. O., Chong, M. M. & Hannon, G. J. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465, 584–589 (2010).
Nakayashiki, H., Kadotani, N. & Mayama, S. Evolution and diversification of RNA silencing proteins in fungi. J. Mol. Evol. 63, 127–135 (2006).
Salomon, W. E., Jolly, S. M., Moore, M. J., Zamore, P. D. & Serebrov, V. Single-molecule imaging reveals that Argonaute reshapes the binding properties of its nucleic acid guides. Cell 162, 84–95 (2015).
Jones-Rhoades, M. W. & Bartel, D. P. Computational identification of plant microRNAs and their targets, including a stress-induced miRNA. Mol. Cell 14, 787–799 (2004).
Niklas, K. J. & Newman, S. A. The origins of multicellular organisms. Evol. Dev. 15, 41–52 (2013).
Trillo, I. R. & Nedelcu, A. M. Evolutionary Transitions to Multicellular Life: Principles and mechanisms Vol. 2 (Springer, 2015).
Michod, R. E. & Roze, D. Cooperation and conflict in the evolution of multicellularity. Heredity 86, 1–7 (2001).
Michod, R. E., Viossat, Y., Solari, C. A., Hurand, M. & Nedelcu, A. M. Life-history evolution and the origin of multicellularity. J. Theor. Biol. 239, 257–272 (2006).
Olsen, P. H. & Ambros, V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev. Biol. 216, 671–680 (1999).
Ambros, V. A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell 57, 49–57 (1989).
Aukerman, M. J. & Sakai, H. Regulation of flowering time and floral organ identity by a microRNA and its APETALA2-like target genes. Plant Cell 15, 2730–2741 (2003).
Chen, Y. & Stallings, R. L. Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 67, 976–983 (2007).
Melton, C., Judson, R. L. & Blelloch, R. Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature 463, 621–626 (2010).
Rosa, A. et al. The interplay between the master transcription factor PU. 1 and miR-424 regulates human monocyte/macrophage differentiation. Proc. Natl Acad. Sci. USA 104, 19849–19854 (2007).
Schoolmeesters, A. et al. Functional profiling reveals critical role for miRNA in differentiation of human mesenchymal stem cells. PLoS ONE 4, e5605 (2009).
Flynt, A. S. & Lai, E. C. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat. Rev. Genet. 9, 831–842 (2008).
Hornstein, E. & Shomron, N. Canalization of development by microRNAs. Nat. Genet. 38, S20–S24 (2006).
Baumgarten, S. et al. Integrating microRNA and mRNA expression profiling in Symbiodinium microadriaticum, a dinoflagellate symbiont of reef-building corals. BMC Genom. 14, 1 (2013).
Ratcliff, W. C. et al. Experimental evolution of an alternating uni-and multicellular life cycle in Chlamydomonas reinhardtii. Nat. Commun. 4, 2742 (2013).
Lee, H.-C. et al. Diverse pathways generate microRNA-like RNAs and Dicer-independent small interfering RNAs in fungi. Mol. Cell 38, 803–814 (2010).
Heimberg, A. M., Sempere, L. F., Moy, V. N., Donoghue, P. C. & Peterson, K. J. MicroRNAs and the advent of vertebrate morphological complexity. Proc. Natl Acad. Sci. USA 105, 2946–2950 (2008).
Sempere, L. F., Cole, C. N., Mcpeek, M. A. & Peterson, K. J. The phylogenetic distribution of metazoan microRNAs: insights into evolutionary complexity and constraint. J. Exp. Zool. Part B 306, 575–588 (2006).
Wheeler, B. M. et al. The deep evolution of metazoan microRNAs. Evol. Dev. 11, 50–68 (2009).
Londin, E. et al. Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs. Proc. Natl Acad. Sci. USA 112, E1106–E1115 (2015).
Putnam, N. H. et al. Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science 317, 86–94 (2007).
Sperling, E. A. et al. MicroRNAs resolve an apparent conflict between annelid systematics and their fossil record. Proc. R. Soc. B 276, 4315–4322 (2009).
Small RNA research in the Moran lab is supported by a European Research Council Starting Grant (CNIDARIAMICRORNA, 637456) and a Young Investigator Grant by the German–Israeli Foundation for Scientific Research and Development (I-1058-203.7-2013). Research in the Technau group is supported by grants of the Austrian Research Fund FWF (P24858 and P22618).
The author declares no competing financial interests.
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Moran, Y., Agron, M., Praher, D. et al. The evolutionary origin of plant and animal microRNAs. Nat Ecol Evol 1, 0027 (2017). https://doi.org/10.1038/s41559-016-0027
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