GROUP LEADER: Fátima Gebauer

LAB MANAGERS: Olga Coll, Tanit Guitart

POSTDOCTORAL RESEARCHERS: Rosario Avolio, Ezequiel Rivero

PhD STUDENTS: Himapriyanka Nadimpali, Marta Inglés, Roísin-Ana Ni Charthaigh, Alberto Indacochea, Neus Mestre

MASTER STUDENT: Adriá Nogales

TECHNICIAN: Anna Ribó

VISITOR: Nele Merret Hollmann

SUMMARY

Our group is interested in post-transcriptional regulation during embryo development and disease. In particular, we investigate how RNA-binding proteins (RBPs) regulate translation and how this is connected with general cell homeostasis and cancer progression. During this year, we have identified new RBPs with roles in melanoma progression, including enzymes with previously unrecognized roles in RNA metabolism, as well as RBPs that have not been related to cancer progression in the past (work in progress). Regarding mechanisms of translational control, using Drosophila as a model system we have identified a role for the RBP Hrp48 in translational repression via connections with eIF3d, a subunit of the multicomponent translation initiation factor eIF3. This work shows how general translation factors can contribute to mRNA-specific translational control. In addition, we have found a novel role for the RNAi factor Dicer-2 in translation stimulation via cytoplasmic polyadenylation.

Model for translational repression of msl-2 mRNA. Repression is orchestrated by a choreography of RBPs. First, SXL binds to both UTRs of the message. SXL bound to the 3’ UTR recruits UNR and interacts with Hrp48. Contacts of these factors with PABP and elF3d contribute to inhibit ribosome recruitment to the mRNA. SXL bound to the 5’ UTR inhibits the scanning of those ribosomal complexes that have escaped the 3’ UTR-mediated control.

Fig. 1

Model for translational repression of msl-2 mRNA. Repression is orchestrated by a choreography of RBPs. First, SXL binds to both UTRs of the message. SXL bound to the 3’ UTR recruits UNR and interacts with Hrp48. Contacts of these factors with PABP and elF3d contribute to inhibit ribosome recruitment to the mRNA. SXL bound to the 5’ UTR inhibits the scanning of those ribosomal complexes that have escaped the 3’ UTR-mediated control.

RESEARCH PROJECTS

  • Identification of RNA binding proteins with roles in melanoma progression
  • Role of UNR/CSDE1 in cell senescence
  • Molecular mechanism of translation regulation by UNR/CSDE1
  • Cytoplasmic polyadenylation in Drosophila
  • Molecular mechanisms of translational repression of Drosophila msl2 mRNA

SELECTED PUBLICATIONS

Szostak E, García-Beyaert M, Guitart T, Graindorge A, Coll O and Gebauer F.
“Hrp48 and eIF3d contribute to msl-2 mRNA translational repression.”
Nucleic Acids Res, 46:4099-4113, 2018.

Coll O, Guitart T, Villalba A, Papin C, Simonelig M and Gebauer F.
“Dicer-2 promotes mRNA activation through cytoplasmic polyadenylation.”
RNA, 24:529-539, 2018.
Faculty1000 recommended

Abdel-Wahab O, Gebauer F.
“Editorial overview: Cancer genomics: RNA metabolism and translation in cancer pathogenesis and therapy.”
Curr Opin Genet Dev, 48:iv-vi, 2018.

Moschall R, Strauss D, Garcia-Bayert M, Gebauer F, Medenbach J.
“Drosophila Sister of Sex-lethal is a repressor of translation.”
RNA, 24:149-158, 2018.