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Structural biology of mRNA localization

Fulvia Bono

Fulvia Bono

  • PhD at the University of Pavia, 2000
  • Postdoctoral training at EMBL Heidelberg, 2002-07
  • Project leader at the MPI, 2008-11
  • Research group leader at the MPI since 2011

Research Interest

The localization of certain mRNAs at specific sites within the cytoplasm plays a crucial role in the development of a wide range of organisms. Such mRNAs are assembled into transport particles that contain multiple copies of the mRNA along with regulatory proteins that allow attachment to motor proteins on the cytoskeleton and direct the mRNAs to their final location. The molecular basis for the assembly of transport particles remains a major unanswered question in the field.

One of the better studied examples of a mRNP component able to influence downstream events in mRNA metabolism is the exon junction complex (EJC), a key regulator of oskar mRNA localization in Drosophila. Structural studies on this complex showed how it maintains a stable grip on the mRNA (Fig. 1) and how cofactors in the cytoplasm might help to disassemble the complex. We are also interested in how EJC components are recycled back to the nucleus in order to be re-incorporated in new mRNPs. This last aspect brought us to study the relatively large molecular assemblies of import-cargo complexes (Fig. 2) and their regulation by RanGTP. We aim to use biochemical and structural methods to study the intermediate states in the EJC cycle to gain a mechanistic understanding of how the system works.

Selected Reading

Bono F, Ebert J, Lorentzen E, Conti E. (2006) The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA. Cell 126, 713-25.

Bono F, Cook A, Grünwald M, Ebert J, Conti E. (2010) Nuclear import mechanism of the EJC component Mago-Y14 revealed by structural studies of Importin13. Mol Cell 37, 211-22.

Grünwald M, Bono F. (2011) Structure of Importin13-Ubc9 complex: nuclear import and release of a key regulator of sumoylation. EMBO J 30, 427-38.
(click to enlarge)
Crystal structure of the exon junction complex (EJC), pdb entries 2j0s, 2j09.
(click to enlarge)
Crystal structure of the import complex of the EJC component Mago-Y14 with Importin13, pdb entry 2x1g.