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Regulation of Maternal mRNA in Early Development by Translation and Localisation

Research Groupings: Structural and molecular cell biology | Developmental and regenerative biology and medicine

Gene expression in early development, at a time when transcription is silent, is essentially regulated at the level of protein synthesis, in a wide variety of organisms.

Proposed model for silencing translation by CPEB in Xenopus oocytes The repression of mRNAs which contain CPE (cytoplasmic polyadenylation) elements in their 3’UTR in Xenopus oocytes by the eIF4E1b/4E-T/CPEB complex is mediated by the combination of conserved P-body components including Xp54 and 4E-T, alongside a weak cap-binding eIF4E protein, which can act as a co-repressor when tethered to the 3’UTR (1).

In Xenopus, when oocytes resume meiosis, specific mRNAs are recruited onto polysomes from a quiescent form. These masked mRNAs encode polypeptides necessary for cell cycle entry and progression, such as c-mos and cyclin B1 mRNAs, and are translationally regulated by CPEB. In oocytes CPEB is present in a very large, P-body like RNP complex, which contains several other RNA-binding proteins including Xp54 RNA helicase, Pat1 and RAP55, as well as an ovary-specific eIF4E cap-binding protein and 4E-T (1). The temporal and spatial regulation of maternal mRNAs also establishes embryonic axes and determines cell fate. One example of a localised Xenopus mRNA, subject to translational control, is Vg1 mRNA (2), which encodes a member of the transforming growth factor β family. Current projects focus on characterising the role of components of the CPEB complex in translational repression, and on identifying small non-coding RNAs including microRNAs in Xenopus oocytes (3). We are also interested in identifying and characterising components of the RNA transport and anchoring machinary, including Vg1RBP and Staufen, and in analysing the link between RNA localisation and translational control of Vg1 mRNA.

Lab members
J Armisen Garrido, Aline Marnef, Nicola Minshall, Anna Wilczynska

Collaborators
Evelyn Houliston, Osvaldo de Melo Meto, Dominique Weil, Eric Miska, Ed Darzynkiewicz

References