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A High-Resolution Structure of the Pre-microRNA Nuclear Export Machinery

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Science  27 Nov 2009:
Vol. 326, Issue 5957, pp. 1275-1279
DOI: 10.1126/science.1178705

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Pre-MicroRNA Export Machinery

Micro (mi) RNAs play a role in the regulation of many biological processes. Long transcripts are initially processed in the nucleus to yield pre-miRNAs that are translocated through the nuclear pore complex and further processed to mature miRNAs in the cytoplasm. Okada et al. (p. 1275; see the Perspective by Stewart) describe the crystal structure of pre-miRNA complexed with the exportin Exp5 and the small nuclear GTPase RanGTP. The structure shows that Exp5 and RanGTP protect the miRNA from degradation by nucleases, as well as facilitate transport to the cytoplasm. RNA recognition is mainly through ionic interactions that are sequence independent, and model-building suggests that this nuclear export machinery could accommodate other small-structured RNAs.

Abstract

Nuclear export of microRNAs (miRNAs) by exportin-5 (Exp-5) is an essential step in miRNA biogenesis. Here, we present the 2.9 angstrom structure of the pre-miRNA nuclear export machinery formed by pre-miRNA complexed with Exp-5 and a guanine triphosphate (GTP)–bound form of the small nuclear guanine triphosphatase (GTPase) Ran (RanGTP). The x-ray structure shows that Exp-5:RanGTP recognizes the 2-nucleotide 3′ overhang structure and the double-stranded stem of the pre-miRNA. Exp-5:RanGTP shields the pre-miRNA stem from degradation in a baseball mitt–like structure where it is held by broadly distributed weak interactions, whereas a tunnel-like structure of Exp-5 interacts strongly with the 2-nucleotide 3′ overhang through hydrogen bonds and ionic interactions. RNA recognition by Exp-5:RanGTP does not depend on RNA sequence, implying that Exp-5:RanGTP can recognize a variety of pre-miRNAs.

  • * These authors contributed equally to this work.

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