eEF1A Mediates the Nuclear Export of SNAG-Containing Proteins via the Exportin5-Aminoacyl-tRNA Complex

Snail proteins are important transcription factors involved in different processes during embryonic development, as well as in several adult pathologies including cancer and organ fibrosis. One efficient way to inactivate transcription factors is to export them out of the nucleus by a process mainly mediated by a family of moelcules called exportins. In this work we show that one of these exportins, Exportin 5 (Exp5), which normally mediates the nuclear export of dsRNA molecules including pre-miRNAs and tRNAs is also able to export transcription factors. This study also shows that the elongation factor eEF1A, crucial for protein biosynthesis in the cytoplasm, plays an important role in the nucleus. It removes Snail factors from their main promoter target, the E-cadherin promoter. EF1A subsequent binding to its natural partner, aatRNA, promotes the export of Snail factors in association with the aatRNA-Exportin5 complex to the cytoplasm, therefore inactivating them as transcription factors. eEF1A binds to Snail proteins through the SNAG domain, also present in other transcription factor families. Thus, we describe a novel protein nuclear export domain (SNAG), a novel protein export complex and reveal a nuclear role for eEF1A, revealing a mechanism for protein nuclear export that attenuates the activity of SNAG-containing transcription factors.