Functional anatomy of the human microprocessor

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

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

MicroRNA (miRNA) maturation is initiated by Microprocessor composed of RNase III DROSHA and its cofactor DGCR8, whose fidelity is critical for generation of functional miRNAs. To understand how Microprocessor recognizes pri-miRNAs, we here reconstitute human Microprocessor with purified recombinant proteins. We find that Microprocessor is an ∼ 364 kDa heterotrimeric complex of one DROSHA and two DGCR8 molecules. Together with a 23-amino acid peptide from DGCR8, DROSHA constitutes a minimal functional core. DROSHA serves as a "ruler" by measuring 11 bp from the basal ssRNA-dsRNA junction. DGCR8 interacts with the stem and apical elements through its dsRNA-binding domains and RNA-binding heme domain, respectively, allowing efficient and accurate processing. DROSHA and DGCR8, respectively, recognize the basal UG and apical UGU motifs, which ensure proper orientation of the complex. These findings clarify controversies over the action mechanism of DROSHA and allow us to build a general model for pri-miRNA processing.

Original languageEnglish
Pages (from-to)1374-1387
Number of pages14
JournalCell
Volume161
Issue number6
DOIs
Publication statusPublished - 2015 Jun 5
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nguyen, T. A., Jo, M. H., Choi, Y. G., Park, J., Kwon, S. C., Hohng, S., Kim, V. N., & Woo, J. S. (2015). Functional anatomy of the human microprocessor. Cell, 161(6), 1374-1387. https://doi.org/10.1016/j.cell.2015.05.010