Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Feb;12(2):172-7.
doi: 10.1038/embor.2010.191. Epub 2011 Jan 7.

MicroRNA evolution by arm switching

Affiliations

MicroRNA evolution by arm switching

Sam Griffiths-Jones et al. EMBO Rep. 2011 Feb.

Abstract

MicroRNAs (miRNAs) modulate transcript stability and translation. Functional mature miRNAs are processed from one or both arms of the hairpin precursor. The miR-100/10 family has undergone three independent evolutionary events that have switched the arm from which the functional miRNA is processed. The dominant miR-10 sequences in the insects Drosophila melanogaster and Tribolium castaneum are processed from opposite arms. However, the duplex produced by Dicer cleavage has an identical sequence in fly and beetle. Expression of the Tribolium miR-10 sequence in Drosophila S2 cells recapitulates the native beetle pattern. Thus, arm usage is encoded in the primary miRNA sequence, but outside the mature miRNA duplex. We show that the predicted messenger RNA targets and inferred function of sequences from opposite arms differ significantly. Arm switching is likely to be general, and provides a fundamental mechanism to evolve the function of a miRNA locus and target gene network.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
The evolution of the miR-100/10 family. miR-10 family members are located in two clusters. Boxes represent the hairpin precursor sequences, with the direction of transcription shown by arrowheads and the dominant mature sequence filled. The left-hand cluster is located in the Hox complex, with Hox genes transcribed from 3′ to 5′ (not shown). Inferred duplication events (blue) are shown by arrows (top) and their evolutionary time is marked on the species tree (left). Arm switches in the ancestral miR-993 (a), Drosophila miR-10 (b), and Ciona miR-1473 (c) are boxed and labelled on the tree (red). Example genomes are shown. Genomic distances are not to scale. B. flo, B. floridae; C. ele, C. elegans; C. int, C. intestinalis; C. tel, C. teleta; D. mel, D. melanogaster; H. sap, H. sapiens; N. vec, N. vectensis; T. cas, T. castaneum.
Figure 2
Figure 2
Arm-specific miRNA processing in miR-100/10 family members. (A) Relative expression of mature miRNAs from 5′ and 3′ arms. Schematic of a precursor hairpin (centre). The relative abundance of the 5′ and 3′ arms of the four miR-100/10 subfamilies is shown, estimated by high-throughput sequencing reads (D. mel; Ruby et al, 2007 and T. cas; supplementary Fig S2 online) and cloning frequencies (H. sapiens; Landgraf et al, 2007). (B) Arm-specific miRNA processing in Drosophila S2 cells. Tribolium and Drosophila miR-10/miR-100 constructs were transfected into S2 cells and expressed under the control of the actin promoter. TaqMan miRNA real-time PCR assays were used to estimate 5′ and 3′ miRNA arm levels. Error bars show the s.e.m. of three technical replicates of three biological experiments. D. mel, D. melanogaster; H. sap, H. sapiens; miRNA, microRNA; T. cas, T. castaneum.
Figure 3
Figure 3
A model of the differential processing of the miR-10 transcript. The precursor miRNA hairpin is excised from the primary miRNA transcript by Drosha. Dicer cleavage yields the mature miRNA duplex, and the dominant arm targets the RNA-induced silencing complex to mRNA transcripts. The sequences of the mature miRNA duplex produced by Dicer cleavage are identical in D. melanogaster and T. castaneum; yet, the 5′ arm (magenta) dominates in Tribolium and the 3′ arm (blue) dominates in Drosophila. The sequence signals controlling arm dominance are therefore outside the mature miRNA duplex, and the arm choice must be specified before Dicer cleavage (that is, above the dotted line). miRNA, microRNA.

References

    1. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136: 215–233 - PMC - PubMed
    1. Bernhart SH, Hofacker IL, Will S, Gruber AR, Stadler PF (2008) RNAalifold: improved consensus structure prediction for RNA alignments. BMC Bioinformatics 9: 474. - PMC - PubMed
    1. Chiang HR et al. (2010) Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. Genes Dev 24: 992–1009 - PMC - PubMed
    1. Czech B, Zhou R, Erlich Y, Brennecke J, Binari R, Villalta C, Gordon A, Perrimon N, Hannon GJ (2009) Hierarchical rules for Argonaute loading in Drosophila. Mol Cell 36: 445–456 - PMC - PubMed
    1. de Wit E, Linsen S, Cuppen E, Berezikov E (2009) Repertoire and evolution of miRNA genes in four divergent nematode species. Genome Res 19: 2064–2074 - PMC - PubMed

Publication types