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Two motifs essential for nuclear import of the hnRNP A1 nucleocytoplasmic shuttling sequence M9 core

Megumi Iijima1, Maiko Suzuki, Ayako Tanabe

  • 1Graduate School of Integrated Science, Yokohama City University, 22-2, Seto, Kanazawa-ku, Yokohama 236-0027, Japan.

FEBS Letters
|February 4, 2006
PubMed

Insights

The M9 core sequence of heterogeneous nuclear ribonucleoprotein A1 is essential for nuclear-cytoplasmic shuttling. The C-terminal PY motif is crucial for nuclear import and transportin binding.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 plays a key role in mRNA genesis.
  • hnRNP A1 shuttles between the nucleus and cytoplasm, a process regulated by its M9 sequence.
  • Understanding hnRNP A1 nucleocytoplasmic transport is crucial for comprehending gene expression regulation.

Purpose of the Study:

  • To investigate the molecular mechanisms governing the nuclear import and export of hnRNP A1 via its M9 shuttling signal.
  • To identify the specific regions and residues within M9 critical for nucleocytoplasmic shuttling and transportin interaction.

Main Methods:

  • Utilized mutational analysis to dissect the function of the M9 sequence.
  • Employed heterokaryon assays to assess nucleocytoplasmic shuttling activity.
  • Investigated the binding of M9 core mutants to transportin.

Main Results:

  • The 19-residue M9 core sequence (SNFGPMKGGNFGGRSSGPY) was found to be necessary and sufficient for hnRNP A1 shuttling.
  • Mutational analysis revealed that both the N-terminal SNFGPMK motif and the C-terminal PY motif are critical for nuclear import.
  • The C-terminal PY motif is essential for binding to the nuclear import receptor, transportin.

Conclusions:

  • The M9 core sequence mediates hnRNP A1 nucleocytoplasmic shuttling.
  • Both N-terminal and C-terminal motifs within M9 are vital for efficient nuclear import and interaction with transportin.
  • Conserved residues in these motifs suggest a conserved mechanism for shuttling in related proteins like hnRNP D and JKTBP.

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