Evolutionary development of redundant nuclear localization signals in the mRNA export factor NXF1

Zi Chao Zhang, Neal Satterly, Beatriz M A Fontoura, Yuh Min Chook

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In human cells, the mRNA export factor NXF1 resides in the nucleoplasm and at nuclear pore complexes. Karyopherin β2 or transportin recognizes a proline-tyrosine nuclear localization signal (PY-NLS) in the N-terminal tail of NXF1 and imports it into the nucleus. Here biochemical and cellular studies to understand the energetic organization of the NXF1 PY-NLS reveal unexpected redundancy in the nuclear import pathways used by NXF1. Human NXF1 can be imported via importin β, karyopherin β2, importin 4, importin 11, and importin α. Two NLS epitopes within the N-terminal tail, an N-terminal basic segment and a C-terminal R-X 2-5-P-Y motif, provide the majority of binding energy for all five karyopherins. Mutation of both NLS epitopes abolishes binding to the karyopherins, mislocalized NXF1 to the cytoplasm, and significantly compromised its mRNA export function. The understanding of how different karyopherins recognize human NXF1, the examination of NXF1 sequences from divergent eukaryotes, and the interactions of NXF1 homologues with various karyopherins reveals the evolutionary development of redundant NLSs in NXF1 of higher eukaryotes. Redundancy of nuclear import pathways for NXF1 increases progressively from fungi to nematodes and insects to chordates, potentially paralleling the increasing complexity in mRNA export regulation and the evolution of new nuclear functions for NXF1.

Original languageEnglish (US)
Pages (from-to)4657-4668
Number of pages12
JournalMolecular Biology of the Cell
Volume22
Issue number23
DOIs
StatePublished - Dec 1 2011

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Karyopherins
Nuclear Localization Signals
Messenger RNA
Cell Nucleus Active Transport
Eukaryota
Proline
Tyrosine
Tail
Epitopes
Chordata
Nuclear Pore
Insects
Cytoplasm
Fungi

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Evolutionary development of redundant nuclear localization signals in the mRNA export factor NXF1. / Zhang, Zi Chao; Satterly, Neal; Fontoura, Beatriz M A; Chook, Yuh Min.

In: Molecular Biology of the Cell, Vol. 22, No. 23, 01.12.2011, p. 4657-4668.

Research output: Contribution to journalArticle

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