Structural biology of mRNA localization

Fulvia Bono

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

Research Interest

The localization of mRNAs is a prominent mode of regulation of gene expression in eukaryotes. Localized RNAs can have crucial roles during animal development, in the maintenance of cell polarity and in nervous system function. Studies of RNA localization in model organisms have revealed many components of the process, some of which are conserved across eukaryotes. The correct cytoplasmic localization of mRNAs and their transport and silencing in messenger ribonucleoprotein particles (mRNPs), is dependent on the earliest steps of mRNA processing in the nucleus. The core nuclear mRNP particles associate with further components in the cytoplasm, forming large and dynamic multimolecular assemblies, underlying the various steps or mRNA maturation, transport, silencing and eventual localized translation. Even though many components of these large mRNP particles are known, their detailed molecular organization and regulation is poorly understood. Our aim is to gather structural information of mRNP complexes involved in RNA localization in the fruit fly Drosophila, currently the best-studied model system. We use a multidisciplinary approach, combining biochemistry, X-ray crystallography and fly genetics, to tackle the complex structure-function relationships regulating mRNA localization. Our goal is to elucidate the structural details and molecular mechanisms of how mRNP complexes regulate mRNA localization during development. Given that mRNA localization is a conserved process, our results are expected to elucidate the mechanistic and structural details of a conserved regulatory pathway with fundamental and often medically relevant roles in the cell.

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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. 1A) and how EJC components are recycled back to the nucleus in order to be re-incorporated in new mRNPs (Fig. 1B).

Available PhD Projects

No projects offered in the 2017 selection.

Selected Reading

1) 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.

2) 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.

3) Kinkelin K, Veith K, Grünwald M and Bono F. (2012) Crystal structure of a minimal eIF4E-Cup complex reveals a general mechanism of eIF4E regulation in translational repression. RNA 18, 1624-34.