Project Leader:Catia Igreja
Department:Biochemistry
Assistant: Maria GölzSibylle Patheiger
Phone:+49 7071 601-1370, +49 7071 601-1360
Fax:+49 7071 601-1353
Staff:Alphabetical List

Introduction

In eukaryotic cells, the production of proteins relies on the action of numerous complexes that coordinate the loading of ribosomes onto mRNAs. The multitude of protein complexes that function during translation allows the selective translation of mRNAs according to the cellular needs. Moreover, regulatory proteins, mRNA features and signalling cues tightly control mRNA translation to avoid unrestrained protein synthesis, a hallmark of several pathophysiological conditions.

We are interested in how different protein complexes assemble and operate in the regulation of translation, particularly at the initiation step. We focus our studies on the function of the eukaryotic translation initiation factor 4F (eIF4F), the diversity of its subunits in cells and the role of its regulatory proteins (such as the eIF4E-binding proteins, 4E-BPs or the eIF4E-homologous protein, 4EHP) and associated factors. Our aim is to provide novel insight into the molecular mechanisms used by specific regulatory proteins or translation complexes to govern protein production. We use an interdisciplinary approach combining molecular and cellular biology (e.g. CRISPR-Cas9-mediated genome-editing, RNA sequencing and ribosome profiling, reporter assays) together with bioinformatics and structural biology expertise already established in the department.

* Co-corresponding author 

2018

Gruner, S., Weber, R., Peter, D., Chung, M.Y., Igreja, C.*, Valkov, E., and Izaurralde, E. Structural motifs in eIF4G and 4E-BPs modulate their binding to eIF4E to regulate translation initiation in yeast. Nucleic Acids Res 46, 6893-6908.

2017

Peter, D., Weber, R., Sandmeir, F., Wohlbold, L., Helms, S., Bawankar, P., Valkov, E., Igreja, C.*, and Izaurralde, E. GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression. Genes Dev 31, 1147-1161.

2016

Grüner, S., Peter, D., Weber, R., Wohlbold, L., Chung, M.Y., Weichenrieder, O., Valkov, E., Igreja, C., and Izaurralde, E. The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation. Mol Cell 64, 467-479.

Greco Hernández, Gillespie, K.M., Bachvaroff, T.R., Jagus, R., Igreja, C., Peter, D., Bulfoni, M., and Cosson, B. Evolution of eIF4E-interacting proteins. In Evolution of the protein synthesis machinery and its regulation, G. Hernández, and R. Jagus, eds. (Springer), pp. 207-234.

2015

Peter, D., Weber, R., Koene, C., Chung, M.Y., Ebertsch, L., Truffault, V., Weichenrieder, O., Igreja, C.*, and Izaurralde, E. Mextli proteins use both canonical bipartite and novel tripartite binding modes to form eIF4E complexes that display differential sensitivity to 4E-BP regulation. Genes Dev. 29, 1835

Peter, D., Igreja, C., Weber R., Wohlbold L., Weiler, C., Ebertsch L., Weichenrieder O., Izaurralde, E. Molecular architecture of 4E-BP translational inhibitors bound to eIF4E. Mol. Cell 57 (6): 1074.

2014

Igreja, C., Peter, D., Weiler, C., Izaurralde, E. 4E-BPs require non-canonical 4E-binding motifs and a lateral surface of eIF4E to repress translation. Nat Commun. 5:4790.

2011

Igreja, C., and Izaurralde, E. CUP promotes deadenylation and inhibits decapping of mRNA targets. Genes Dev 25, 1955-1967.