Role of pri-miRNA tertiary structure in miR-17∼92 miRNA biogenesis

Steven G. Chaulk, Gina L. Thede, Oliver A. Kent, Zhizhong Xu, Emily M. Gesner, Richard A. Veldhoen, Suneil K. Khanna, Ing Swie Goping, Andrew M. MacMillan, Joshua T. Mendell, Howard S. Young, Richard P. Fahlman, J. N Mark Glover

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) regulate gene expression in a variety of biological pathways such as development and tumorigenesis. miRNAs are initially expressed as long primary transcripts (pri-miRNAs) that undergo sequential processing by Drosha and then Dicer to yield mature miRNAs. miR-17∼92 is a miRNA cluster that encodes 6 miRNAs and while it is essential for development it also has reported oncogenic activity. To date, the role of RNA structure in miRNA biogenesis has only been considered in terms of the secondary structural elements required for processing of pri-miRNAs by Drosha. Here we report that the miR-17∼92 cluster has a compact globular tertiary structure where miRNAs internalized within the core of the folded structure are processed less efficiently than miRNAs on the surface of the structure. Increased miR- 92 expression resulting from disruption of the compact miR-17∼92 structure results in increased repression of integrin α5 mRNA, a known target of miR-92a. In summary, we describe the first example of pri-miRNA structure modulating differential expression of constituent miRNAs.

Original languageEnglish (US)
JournalRNA Biology
Volume8
Issue number6
DOIs
StatePublished - Nov 2011

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MicroRNAs
Integrins
Carcinogenesis
RNA
Gene Expression
Messenger RNA

Keywords

  • Drosha
  • miRNA biogenesis
  • miRNA cluster
  • Pri-miRNA structure

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Chaulk, S. G., Thede, G. L., Kent, O. A., Xu, Z., Gesner, E. M., Veldhoen, R. A., ... Glover, J. N. M. (2011). Role of pri-miRNA tertiary structure in miR-17∼92 miRNA biogenesis. RNA Biology, 8(6). https://doi.org/10.4161/rna.8.6.17410

Role of pri-miRNA tertiary structure in miR-17∼92 miRNA biogenesis. / Chaulk, Steven G.; Thede, Gina L.; Kent, Oliver A.; Xu, Zhizhong; Gesner, Emily M.; Veldhoen, Richard A.; Khanna, Suneil K.; Goping, Ing Swie; MacMillan, Andrew M.; Mendell, Joshua T.; Young, Howard S.; Fahlman, Richard P.; Glover, J. N Mark.

In: RNA Biology, Vol. 8, No. 6, 11.2011.

Research output: Contribution to journalArticle

Chaulk, SG, Thede, GL, Kent, OA, Xu, Z, Gesner, EM, Veldhoen, RA, Khanna, SK, Goping, IS, MacMillan, AM, Mendell, JT, Young, HS, Fahlman, RP & Glover, JNM 2011, 'Role of pri-miRNA tertiary structure in miR-17∼92 miRNA biogenesis', RNA Biology, vol. 8, no. 6. https://doi.org/10.4161/rna.8.6.17410
Chaulk SG, Thede GL, Kent OA, Xu Z, Gesner EM, Veldhoen RA et al. Role of pri-miRNA tertiary structure in miR-17∼92 miRNA biogenesis. RNA Biology. 2011 Nov;8(6). https://doi.org/10.4161/rna.8.6.17410
Chaulk, Steven G. ; Thede, Gina L. ; Kent, Oliver A. ; Xu, Zhizhong ; Gesner, Emily M. ; Veldhoen, Richard A. ; Khanna, Suneil K. ; Goping, Ing Swie ; MacMillan, Andrew M. ; Mendell, Joshua T. ; Young, Howard S. ; Fahlman, Richard P. ; Glover, J. N Mark. / Role of pri-miRNA tertiary structure in miR-17∼92 miRNA biogenesis. In: RNA Biology. 2011 ; Vol. 8, No. 6.
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