Internal Initiation of Translation
E. Martinez-Salas laboratory has played a leadership role in the translation control field. Her publication track record includes 114 articles (PubMed), and she is Principal Investigator of 25 competitive grants. Her PhD studies were focused to E. coli cell division genes. She did a postdoctoral period focused on RNA virus genetic variability, and then on transcriptional control in early mouse embryos. Since 1995 she is the Principal Investigator of the group working on Internal initiation of translation at the CBMSO. She has supervised the work 14 postdoctoral students, 10 PhD students, and 21 Master students and undergraduate students. She currently supervises the work of 2 postdocts, 1 PhD student and 1 laboratory technician.
Her main achievements are the identification of the role of enhancers in transcriptional activation in early mouse embryos, the structural and functional analysis of viral internal ribosome entry site (IRES) elements, the functional and structural characterization of RNA-binding proteins (RBPs). Her current research interests are focused to understanding mechanisms of translation initiation in eukaryotic cells, functional and structural characterization of RBPs, alternative mechanisms of protein synthesis, and host-factor interactions in infected cells.
- Rosario Francisco Velilla
- Azman Embarc-Buh
- Jorge Ramajo Alonso
- Salvador Abellan Perez
Our aims are focused to understand the principles guiding alternative mechanisms of translation initiation in eukaryotes through the characterization of RNA-binding proteins (RBPs) interacting with mRNAs. Internal ribosome entry sites (IRES) are non-coding RNA regions that substitute the function of the 5’ terminal cap of mRNAs, the anchoring point of the translation machinery. Our specific aims are the identification of proteins modulating IRES activity, the evaluation of synergism and/or interference with other factors, and the understanding of structural constraints which are essential for its activity. Gemin5 is a multitasking protein that forms part of the survival of motor neuron (SMN) complex and performs a regulatory role in translation. Defects on the SMN complex levels lead to SMA (Spinal muscular atrophy), an autosomal rare disease, different from those associated to Gemin5 variants found in patients with neurological disorders. The N-terminal domain of Gemin5 interacts with the ribosome and the snRNAs, whereas the C-terminal region harbors a non-conventional RNA-binding site (RBS1). Identification of the RNA partners of the RBS1 domain unveiled a feedback loop with its own mRNA, counteracting the negative effect of Gemin5 on translation. The RBS1 moiety harbors an intrinsically disordered region (IDR) that comprises a cluster of aromatic residues involved in RNA binding. Additionally, the midle region of the protein harbors a dimerization domain. The crystal structure of this domain consists of a tetratricopeptide (TPR)-like domain that self-assembles into a canoe-shaped dimer. The dimerization module is functional in living cells, providing the basis for a role of Gemin5 as a hub for protein-protein interactions ultimately affecting its role in RNA-dependent processes.