Clarification of Mechanism Underlying Selective Export of MicroRNA, a Protein Synthesis Inhibitor - X-ray crystallography of a complex functioning in pre-microRNA nuclear export (Press Release)
- Release Date
- 27 Nov, 2009
- BL44XU (Macromolecular Assemblies)
Osaka University
University of Hyogo
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A joint research team consisting of researchers from the University of Hyogo, Osaka University, and Chungbuk National University (Korea) has clarified using SPring-8 the mechanism underlying the selective export of microRNAs (miRNAs) that inhibit protein synthesis. In human cells, tens of thousands of types of protein support life. Such proteins are not always required in various life-supporting activities, and their synthesis is inhibited when they are not necessary. miRNAs are involved in the inhibition of protein synthesis, and this inhibition by miRNAs is called RNA interference. Owing to the importance of its role, the scientists who discovered RNA interference were awarded the 2006 Nobel Prize in Medicine. Pre-miRNAs, i.e., precursors of miRNAs, are synthesized in the nucleus. Pre-miRNAs are exported from the nucleus to the cytoplasm as a complex, and then cleaved into two parts, one of which becomes miRNA. Pre-miRNAs are exported from the nucleus to the cytoplasm by two types of protein, i.e., exportin-5 (Exp-5) and guanine triphosphatase Ran (RanGTP). In this research, the nuclear structure where Exp-5, RanGTP, and pre-miRNA are bound (Fig. 4) was determined using the X-rays produced by the SPring-8 Macromolecular Assemblies Beamline, BL44XU, which is a contract beamline for the Institute for Protein Research of Osaka University. The Exp-5:RanGTP complex holds the pre-miRNA double stranded helix, similarly to a baseball caught in a catcher's mitt, and tightly binds to two bases at the end of a single strand. Numerous RNAs are synthesized in the nucleus, and approximately 700 types of pre-miRNA involved in RNA interference have been identified in human cells. In this structural analysis, it was clarified that the Exp-5:RanGTP complex can selectively export only these 700 types of pre-miRNA from the nucleus to the cytoplasm. Owing to this role of the complex, RNA interference proceeds efficiently. Some miRNAs were found to be associated with the development of a certain type of cancer and the proliferation of hepatitis C and AIDS viruses; therefore, the findings of this research may contribute to the prevention and development of treatment strategies for such diseases based on the control of miRNA functions. These results were published in the American scientific journal, Science, on 27 November 2009. Publication: |
Fig. 1 Inhibition of protein synthesis by miRNA (RNA interference)
Fig. 2 Crystal of Exp-5:RanGTP:pre-miRNA complex
Crystallization was realized after four years of research.
Fig. 3 X-ray diffraction image obtained using X-rays at SPring-8
Fig. 4 Steric structure of Exp-5:RanGTP:pre-miRNA complex
Red, Exp-5; Purple, RanGTP; Blue, pre-miRNA
The Exp-5:RanGTP complex holds the pre-miRNA double stranded helix, similarly to a baseball caught in a catcher's mitt, tightly binding to two bases at the end of a single strand. Animation of this is available at the website below.
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