Structure of Human DROSHA

S. Chul Kwon, Tuan Anh Nguyen, Yeon Gil Choi, Myung Hyun Jo, Sungchul Hohng, V. Narry Kim, Jae Sung Woo

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80 Citations (Scopus)

Abstract

MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary microRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring "ruler" activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary microRNA processing.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalCell
Volume164
Issue number1-2
DOIs
Publication statusPublished - 2016 Jan 14
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kwon, S. C., Nguyen, T. A., Choi, Y. G., Jo, M. H., Hohng, S., Kim, V. N., & Woo, J. S. (2016). Structure of Human DROSHA. Cell, 164(1-2), 81-90. https://doi.org/10.1016/j.cell.2015.12.019