Evolutionary Origin of MicroRNAs

Abstract

MicroRNAs (miRNAs) are small RNAs that regulate gene expression and are involved in crucial cellular functions such as development, metabolism and disease. While the biogenesis pathway leading to the formation of functional miRNAs is relatively well understood, the evolutionary origin of miRNAs remains controversial. In the past 10 years, a marked amount of computational and more recently experimental evidence points to an original formation of many miRNAs from transposable elements (TEs). Thousands of miRNAs have been shown to have striking sequence similarity with a wide range of TEs, and the genomic events resulting in the formation of many of these miRNAs have now been well described. This article primarily focusses on the origins of miRNAs and the relationship between miRNAs and TEs summarising the evidence supporting the existence and relevance of TE‐derived miRNAs followed by an examination of the implications of a TE origin for miRNA regulations in target prediction.

Key Concepts

  • MiRNAs are important regulators of gene expression.
  • Many miRNAs were formed from TEs.
  • The transcripts of the gene targets of the TE‐derived miRNAs contain 3′ UTR sequences that have sequence homology to TEs.
  • Experiments confirmed that TE‐derived miRNAs are functional and can regulate gene expression using the same mechanism as non‐transposable element‐derived miRNAs.
  • Taxa‐specific miRNAs can be identified by analysing taxa‐specific TEs.
  • The formation of miRNAs from TEs may have played an important role during evolution of organisms including the development of complex organisms.

Keywords: microRNA; miRNA; transposable element; repetitive; transposon

Figure 1. Timeline of published reports linking miRNA origins to TEs. Twenty‐five papers covering nearly a decade are shown in chronological order. Adapted with permission from Roberts et al. (2014) © Taylor & Francis LLC.
Figure 2. Models of microRNA formation. (a) MiRNA formation typically results when two complementary TEs insert into opposite strands and are then transcribed together. A miRNA hairpin is shown above an arrow denoting read through transcription into a neighbouring negative strand TE. The resulting RNA hairpin could well be recognised and processed via the RNAi machinery making each stem corresponds to the terminal nts of the TEs. (b) Illustration depicting the effects of a point mutation to a tRNA secondary structure. The thermodynamically most stable structures of two tRNAs differing only by the nucleotide found at position 50 are shown. Thermodynamic stabilities and structures were calculated using Mfold (Zuker, ). Adapted with permission from Roberts et al. (2013) © Taylor & Francis LLC.
Figure 3. Illustration depicting miRNA regulatory network formation. As described in Figurea, random TE insertions into the genome at neighbouring positions can lead to the formation of miRNAs. During the extensive period of time it would take for this event to occur the same TE also likely inserted into non‐coding regions of protein‐coding transcripts elsewhere in the genome. As illustrated, this series of events can result in the formation of a network of genes capable of regulation by the TE‐derived miRNA. Adapted with permission from Roberts et al. (2014) © Taylor & Francis LLC.
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Further Reading

Borchert GM, Lanier W and Davidson BL (2006) RNA polymerase III transcribes human microRNAs. Nature Structural & Molecular Biology 13: 1097–1101.

Borchert GM, Holton NW, Williams JD, et al. (2011) Comprehensive analysis of microRNA genomic loci identifies pervasive repetitive‐element origins. Mobile Genetic Elements 1: 8–17.

Filshtein TJ, Mackenzie CO, Dale MD, et al. (2012) OrbId: Origin‐based identification of microRNA targets. Mobile Genetic Elements 2: 184–192.

Roberts JT, Cardin SE and Borchert GM (2014) Burgeoning evidence indicates that microRNAs were initially formed from transposable element sequences. Mobile Genetic Elements 4: e29255.

Roberts JT, Cooper EA, Favreau CJ, et al. (2013) Continuing analysis of microRNA origins: formation from transposable element insertions and noncoding RNA mutations. Mobile Genetic Elements 3: e27755.

Smalheiser NR and Torvik VI (2005) Mammalian microRNAs derived from genomic repeats. Trends in Genetics: TIG 21: 322–326.

Smalheiser NR and Torvik VI (2006) Alu elements within human mRNAs are probable microRNA targets. Trends in Genetics: TIG 22: 532–536.

Spengler RM, Oakley CK and Davidson BL (2014) Functional microRNAs and target sites are created by lineage‐specific transposition. Human Molecular Genetics 23: 1783–1793.

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How to Cite close
Chevalier, David, Roberts, Justin T, and Borchert, Glen M(Nov 2015) Evolutionary Origin of MicroRNAs. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026316]