The DGCR8 RNA-binding heme domain recognizes primary microRNAs by clamping the hairpin
| Autor: | Feng Guo, Grant M. Shoffner, Rachel Senturia, Jose Jacob, Jen Quick-Cleveland, Sara H. Weitz |
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| Rok vydání: | 2014 |
| Předmět: |
Protein Structure
DGCR8 Protein Conformation 1.1 Normal biological development and functioning Medical Physiology RNA-binding protein Heme Biology General Biochemistry Genetics and Molecular Biology Article Microprocessor complex chemistry.chemical_compound Protein structure Underpinning research Genetics Humans lcsh:QH301-705.5 Drosha Nuclease Binding Sites RNA RNA-Binding Proteins Protein Structure Tertiary MicroRNAs lcsh:Biology (General) chemistry Biochemistry Biophysics biology.protein Nucleic Acid Conformation Biochemistry and Cell Biology Tertiary Protein Binding Biotechnology |
| Zdroj: | Cell reports, vol 7, iss 6 Cell Reports, Vol 7, Iss 6, Pp 1994-2005 (2014) Quick-Cleveland, J; Jacob, JP; Weitz, SH; Shoffner, G; Senturia, R; & Guo, F. (2014). The DGCR8 RNA-Binding Heme Domain Recognizes Primary MicroRNAs by Clamping the Hairpin. Cell Reports, 7(6), 1994-2005. doi: 10.1016/j.celrep.2014.05.013. UCLA: Retrieved from: http://www.escholarship.org/uc/item/2rw6m6jt |
| Popis: | Canonical primary microRNA transcripts (pri-miRNAs) are characterized by a ~30bp hairpin flanked by single-stranded regions. These pri-miRNAs are recognized and cleaved by the Microprocessor complex consisting of the Drosha nuclease and its obligate RNA-binding partner DGCR8. It is not well understood how the Microprocessor specifically recognizes pri-miRNA substrates. Here, we show that in addition to the well-known double-stranded RNA-binding domains, DGCR8 uses a dimeric heme-binding domain to directly contact pri-miRNAs. This RNA-binding heme domain (Rhed) directs two DGCR8 dimers to bind each pri-miRNA hairpin. The two Rhed-binding sites are located at both ends of the hairpin. The Rhed and its RNA-binding surface are important for pri-miRNA processing activity. Additionally, the heme cofactor is required for formation of processing-competent DGCR8-pri-miRNA complexes. Our study reveals a unique protein-RNA interaction central to pri-miRNA recognition. We propose a unifying model in which two DGCR8 dimers clamp a pri-miRNA hairpin using their Rheds. © 2014 The Authors. |
| Databáze: | OpenAIRE |
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