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Nuclear import receptors and hnRNPK mediates nuclear import and stress granule localization of SIRLOIN

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Abstract

The majority of lncRNAs and a small fraction of mRNAs localize in the cell nucleus to exert their functions. A SIRLOIN RNA motif was previously reported to drive its nuclear localization by the RNA-binding protein hnRNPK. However, the underlying mechanism remains unclear. Here, we report crystal structures of hnRNPK in complex with SIRLOIN, and with the nuclear import receptor (NIR) Impα1, respectively. The protein hnRNPK bound to SIRLOIN with multiple weak interactions, and interacted Impα1 using an independent high-affinity site. Forming a complex with hnRNPK and Impα1 was essential for the nuclear import and stress granule localization of SIRLOIN in semi-permeabilized cells. Nuclear import of SIRLOIN enhanced with increasing NIR concentrations, but its stress granule localization peaked at a low NIR concentration. Collectively, we propose a mechanism of SIRLOIN localization, in which NIRs functioned as drivers/regulators, and hnRNPK as an adaptor.

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The structure factor and atomic coordinates have been deposited in the Protein Data Bank (PDB) with accession codes 7CRE and 7CRU.

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Acknowledgements

We thank the beamline staff from SSRF beamline BL17U1 [53] and Dr. Rundong Zhang (SKLB) for help in RNA transcription. This study was supported by the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University.

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Authors and Affiliations

  1. Department of Pathology, State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, and Collaborative Innovation Centre of Biotherapy, Chengdu, 610041, China

    Jialin Yao, Congcong Shen, Qiao Zhou & Qingxiang Sun

  2. Division of Neurology, Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, 610041, China

    Yingfeng Tu & Da Jia

  3. Aging Research Lab, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, and Collaborative Innovation Centre of Biotherapy, Chengdu, 610041, China

    Hengyi Xiao

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  1. Jialin Yao
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Contributions

Conceptualization: QS, Methodology: QS, JY, YT, CS, Investigation: JY, QS, Visualization: QS, JY, Supervision: QS, QZ, HX, DJ, YT, Writing—original draft: QS, JY, Writing—review and editing: QS.

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Correspondence to Qingxiang Sun.

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Yao, J., Tu, Y., Shen, C. et al. Nuclear import receptors and hnRNPK mediates nuclear import and stress granule localization of SIRLOIN. Cell. Mol. Life Sci. 78, 7617–7633 (2021). https://doi.org/10.1007/s00018-021-03992-7

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