Weibel-Palade bodies and Golgi apparatus

Andres Ramos group project:

Integration of mRNA metabolism and signalling pathways

Post-transcriptional regulation of gene expression allows modulation of protein synthesis in a fast and localised fashion (Besse F et al, 2008). Information from signalling networks is fed into post-transcriptional regulatory ones by phosphorylation and methylation of the proteins that regulate mRNA metabolism. The addition of a phosphate group has been reported to cause inter-domain rearrangement, protein sequestering and loss of RNA binding capability, leading to changes in mRNA transport and degradation but also in translational repression/activation. We do not yet possess a clear molecular rationale for most of these changes.

We study the molecular features of the post-translational regulation of proteins involved in mRNA decay, mRNA transport and translational repression. We dissect the changes in protein structure and dynamics taking place upon protein phosphorylation and analyse their effect on the protein activity (Díaz-Moreno et al, 2009) (Figure 4). Our aim is to build a repertoire of mechanims used by signalling factors in the tuning of mRNA metabolism.

Figure 4

Figure 4

Click image to view at full-size

Superimposition of the fingerprint ¹⁵N-¹H correlation spectra of wt KSRP KH1 domain, before and after phosphorylation by AKT, and after de-phosphorylation by a phosphatase. The protein unfolds upon AKT phosphorylation and re-folds upon removal of the phosphate group. Phospho-mediated conformational trapping leads to 14-3-3 binding and nuclear localisation.

Selected publications

Ramos group

Recent publications

Research projects

Ramos biography

External links

Top of page

© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA