The RNA-binding protein HuR binds to AU-rich elements in target mRNAs and stabilizes them against degradation. The complete spectrum of genes whose expression is regulated by HuR and thus the basis for the broad range of cellular functions of the protein are incompletely understood. We show that HuR controls the expression of multiple components of the nuclear import machinery. Consequently, HuR is critical for the nuclear import of cellular retinoic acid-binding protein 2 (CRABP2), which delivers RA to the nuclear receptor RAR and whose mobilization to the nucleus is mediated by a ‘classical-like’ nuclear localization signal (NLS). HuR is also required for heregulin-induced nuclear translocation of the NFκB subunit p65, which contains both classical and non-canonical NLS. HuR thus regulates the transcriptional activities of both RAR and NFκB. The observations reveal that HuR plays a central role in regulating protein nuclear import.
- Received May 6, 2016.
- Accepted September 2, 2016.
- © 2016. Published by The Company of Biologists Ltd