Françoise Stutz - Director

Role of ubiquitination in the regulation of mRNP dynamics and export

The different steps involved in the biogenesis and translocation of mRNAs through nuclear pores (NPC) are tightly linked. RNA polymerase II plays a central role in all these events, as it mediates the recruitment of factors involved in mRNA processing and export. All these molecular couplings are monitored by surveillance mechanisms ensuring that only fully mature and functional mRNP particles reach the cytoplasm.

Our previous studies have focused on the evolutionarily conserved export receptor Mex67 and on the adaptor proteins mediating the recruitment of Mex67 to to transcribing genes and nascent mRNPs (Gwizdek, Iglesias et al., 2006; Dieppois et al., 2006). Our current work addresses the role of ubiquitin and specific E3 ligases in the co-transcriptional assembly of export competent mRNP complexes, whether different E3 ligases act in distinct export pathways and whether mRNP rearrangements may be linked to quality control mechanisms (Iglesias and Stutz, 2008; Figure 1).

Figure 1: Functional coupling and mRNP dynamics along the mRNA export pathway. Current work focuses on the ubiquitination of various export factors including the adaptor protein Yra1. Modification of Yra1 by the ubiquitin E3 ligase Tom1 results in its dissociation from the mRNP before export. This event may occur in association with Mlp1/2 at the pore and act as a license for export.