Bidirectional processing of pri-miRNAs with branched terminal loops by Arabidopsis Dicer-like1

Hongliang Zhu, Yuyi Zhou, Claudia Castillo-González, Amber Lu, Chunxiao Ge, Ying Tao Zhao, Liusheng Duan, Zhaohu Li, Michael J. Axtell, Xiu Jie Wang, Xiuren Zhang

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Abstract

MicroRNAs (miRNAs) originate from primary transcripts (pri-miRNAs) with characteristic stem-loop structures, and their accurate processing is required for the production of functional miRNAs. Here, using the pri-miR-166 family in Arabidopsis thaliana as a paradigm, we report the crucial role of pri-miRNA terminal loops in miRNA biogenesis. We found that multibranched terminal loops in pri-miR-166s substantially suppress miR-166 expression in vivo. Unlike canonical processing of pri-miRNAs, terminal loop-branched pri-miRNAs can be processed by Dicer-like 1 (DCL1) complexes bidirectionally from base to loop and from loop to base, resulting in productive and abortive processing of miRNAs, respectively. In both cases, DCL1 complexes canonically cut pri-miRNAs at a distance of 16-17 bp from a reference single-stranded loop region. DCL1 also adjusts processing sites toward an internal loop through its helicase domain. These results provide new insight into the poorly understood processing mechanism of pri-miRNAs with complex secondary structures.

Original languageEnglish (US)
Pages (from-to)1106-1115
Number of pages10
JournalNature Structural and Molecular Biology
Volume20
Issue number9
DOIs
StatePublished - Sep 1 2013

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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    Zhu, H., Zhou, Y., Castillo-González, C., Lu, A., Ge, C., Zhao, Y. T., Duan, L., Li, Z., Axtell, M. J., Wang, X. J., & Zhang, X. (2013). Bidirectional processing of pri-miRNAs with branched terminal loops by Arabidopsis Dicer-like1. Nature Structural and Molecular Biology, 20(9), 1106-1115. https://doi.org/10.1038/nsmb.2646