Molecular Biology

Export Examined

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Science  04 Mar 2011:
Vol. 331, Issue 6021, pp. 1115
DOI: 10.1126/science.331.6021.1115-c

Many RNAs made in the cell nucleus function in the cytoplasm and so must be exported from the nucleus. Pre-microRNAs (pre-miRNAs) are exported from the nucleus via the karyopherin exportin-5 and are processed to their mature (miRNA) form in the cytoplasm by the Dicer protein, where they play a critical role in regulating gene expression. Bennasser et al. find that export of the Dicer mRNA from the nucleus of human cells also requires exportin-5 protein. The expression of exportin-5 is limiting, and overexpression of a substrate miRNA is able to saturate the exportin-5 export pathway. This leads to a decreased association between exportin-5 and its other substrates—such as the Dicer mRNA, which results in reduced amounts of Dicer protein in the cell. Thus, there is cross-regulation between pre-miRNAs and their processing enzyme, Dicer, which could help balance the amounts of the enzyme and its substrate.

Upon infection, adenovirus produces large quantities of two small structured RNAs, which are exported by exportin-5 and can saturate the export pathway and reduce Dicer expression. Knockdown of either exportin-5 or Dicer enhances the growth of a replication-defective adenovirus, hinting that pathogens might also be able to exploit the regulation of Dicer mRNA levels by exportin-5 and, as a result, miRNA and siRNA levels.

Nat. Struct. Mol. Biol. 18, 10.1038/nsmb.1987 (2011).

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