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Research Paper

Selectivity of Exportin 5 binding to human precursor microRNAs

, , , &
Pages 730-737 | Received 12 May 2021, Accepted 15 Sep 2021, Published online: 30 Sep 2021
 

ABSTRACT

Exportin 5 (Exp5, XPO5) is a nuclear export factor that functions in the microRNA (miRNA) biogenesis pathway to transport precursor miRNAs (pre-miRNAs) from the nucleus to the cytoplasm. Most of our current understanding of the Exp5 and pre-miRNA interaction is based on the investigation of how Exp5 binds to human pre-miR-30a (pre-miR-30 for short). As there are hundreds of human miRNA genes, how representative pre-miR-30 is, whether or how Exp5 interacts with distinct cargoes differentially, or whether Exp5 regulates miRNA expression, is unknown. Here we examined and compared the interactions between Exp5 and 157 human pre-miRNAs. We found that Exp5 binds distinct pre-miRNAs with modest variations in efficiencies, with the 3ʹ overhang and the apical loop in pre-miRNAs being the two major discriminating factors. Exp5 binding efficiencies do not significantly correlate with endogenous miRNA expression, suggesting that Exp5 activity does not contribute to differential miRNA expression in vivo. Nonetheless, in human cells with reduced Exp5 levels, preferential Exp5 binding correlated with miRNA expression changes. Thus, our study provides a global picture of how Exp5 interacts with human pre-miRNAs and its role in regulating miRNA expression.

Abbreviations: Exp5: Exportin 5; miRNA: microRNA; pri-miRNA: primary microRNA; pre-miRNA: precursor microRNA; nt: nucleotide

Acknowledgments

We thank Wenjing Li, Min Hu, and Qiuhuan Tian for technical assistance.

Disclosure statement

The authors declare no conflict of interest.

Data availability

The datasets generated during the current study are available in the Gene Expression Omnibus database under the accession number GSE174061.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported in part by the National Natural Science Foundation of China (31570843).

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