Tracking a refined eIF4E-binding motif reveals Angel1 as a new partner of eIF4E.

Pauline Gosselin (1) , Yvan Martineau (2) , Julia Morales (1, 3) , Mirjam Czjzek (3, 4) , Virginie Glippa (1, 3) , Isabelle Gauffeny (1) , Emmanuelle Morin (5) , Gildas Le Corguillé (6) , Stephane Pyronnet (2) , Patrick Cormier (1, 3) , Bertrand Cosson (1, 3)

1 MS - Mer et santé
2 I2MR - Institut de médecine moléculaire de Rangueil
3 LBI2M - Laboratoire de Biologie Intégrative des Modèles Marins
4 Végétaux marins et biomolécules
5 CEISAM - Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation
6 SBR - Station biologique de Roscoff [Roscoff]

The initiation factor 4E (eIF4E) is implicated in most of the crucial steps of the mRNA life cycle and is recognized as a pivotal protein in gene regulation. Many of these roles are mediated by its interaction with specific proteins generally known as eIF4E-interacting partners (4E-IPs), such as eIF4G and 4E-BP. To screen for new 4E-IPs, we developed a novel approach based on structural, in silico and biochemical analyses. We identified the protein Angel1, a member of the CCR4 deadenylase family. Immunoprecipitation experiments provided evidence that Angel1 is able to interact in vitro and in vivo with eIF4E. Point mutation variants of Angel1 demonstrated that the interaction of Angel1 with eIF4E is mediated through a consensus eIF4E-binding motif. Immunofluorescence and cell fractionation experiments showed that Angel1 is confined to the endoplasmic reticulum and Golgi apparatus, where it partially co-localizes with eIF4E and eIF4G, but not with 4E-BP. Furthermore, manipulating Angel1 levels in living cells had no effect on global translation rates, suggesting that the protein has a more specific function. Taken together, our results illustrate that we developed a powerful method for identifying new eIF4E partners and open new perspectives for understanding eIF4E-specific regulation.

Domains: Life Sciences [q-bio]

Pauline Gosselin, Yvan Martineau, Julia Morales, Mirjam Czjzek, Virginie Glippa, et al.. Tracking a refined eIF4E-binding motif reveals Angel1 as a new partner of eIF4E.. Nucleic Acids Research, 2013, 41 (16), pp.7783-92. ⟨10.1093/nar/gkt569⟩. ⟨hal-01002440⟩