mRNA translation at nuclear pores

How do proteins reach their final destination in compartmentalized cells? Researchers from the Palancade team have combined RNA biochemistry and imaging approaches to gain insight into the processes that ensure protein delivery to the nucleus. In their study published this month in Molecular Cell, they reveal that a subset of proteins entering the nucleus are actually translated at nuclear pore complexes, through a mechanism involving the recognition of their nascent chains by nuclear transport receptors.

While it had been known for decades that localized mRNA translation is coupled with protein targeting to intracellular compartments, e.g. the endoplasmic reticulum or the mitochondria, it was commonly accepted that nuclear proteins are imported through nuclear pore complexes (NPC) in a translation-independent manner. This dogma is now challenged by a study led by researchers from the “RNA biogenesis and genome homeostasis” group at IJM, in collaboration with the ProteoSeine facility, the University of Geneva, Sorbonne Université and Institut Curie.  By combining systematic RNA immunoprecipitation and single molecule RNA imaging in yeast, they uncovered that certain nucleoplasmically-oriented NPC subunits, together with a subset of nuclear proteins, are translated from mRNA molecules associated with nuclear pores. Mechanistically, localized translation is achieved by virtue of interactions between nuclear targeting determinants present in the N-termini of nascent polypeptides and NPC-bound nuclear transport receptors of the karyopherin family. Uncoupling mRNA translation from NPC localization further triggers the formation of cytoplasmic foci of the corresponding polypeptides, revealing that NPC-associated translation is required for proper protein targeting to the pore and to the nucleus. Localized translation can thereby also occur at nuclear pores, and further contribute to the homeostasis of the nuclear proteome. Co-translational protein import would thus be a shared feature of distinct membrane-bound translocation machineries, despite their independent evolutionary trajectories.

For more information :

Co-translational assembly and localized translation of nucleoporins in nuclear pore complex biogenesis”

Lautier O, Penzo A, Rouviere JO, Chevreux G, Collet L, Loiodice I, Taddei A, Devaux F, Collart MA & Palancade B

Molecular Cell. Published online: April 9, 2021 LIEN

INSB (CNRS) release: LIEN

Contact : Benoit Palancade, « RNA biogenesis and genome homeostasis » group, benoit.palancade(at)ijm.fr

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