We study the control of translation and mRNA decay in Xenopus early development (when there is no transcription) and in mammalian tissue culture cells. Our main current focus is to characterise the contributions to such control of highly conserved regulatory factors, common to large mRNP containing stored maternal mRNA and to somatic P-(rocessing bodies). P-bodies are distinct cytoplasmic foci which harbour untranslated mRNA which may undergo decay or return to translation, microRNAs and RNA-binding proteins, the cap-binding translation initiation protein eIF4E and its interacting factor, 4E-T. We use a variety of molecular and cell biology techniques (see Figure panels for a selection) to investigate the role in gene expression control of such factors including CPEB, p54 RNA helicase, Pat1, 4E-T and its interactions with canonical and non-canonical cap-binding proteins. The binding sites of many RNA-binding proteins, such as CPEB, and microRNAs, reside in the 3’ untranslated regions of regulated mRNAs, and the assembly of protein complexes at the distal end of the 5’ cap influences translation initiation, mRNA decay as well as mRNA localisation. We are interested in dissecting the relative contributions of the conserved CPEB RNP/P-body factors to these control mechanisms.
Lab members: Helen Broomhead, Anastasiia Kamenska, Demetrios Lucena Sampaio, Clare Simpson
1. Minshall, N., Kress, M., Weil, D. and Standart, N. (2009). Role of p54 RNA helicase activity and its C-terminal domain in translational repression, P-body localization and assembly. Mol. Biol. Cell, 20:2464-2472
2. Armisen, J., Gilchrist, M.J., Wilczynska, A., Standart, N. and Miska, E.A. (2009). Abundant and dynamically expressed miRNAs, endo-RNAs and piRNAs in the African clawed frog Xenopus tropicalis. Genome Res., 19:1766-1775
3. Wilczynska A, Minshall N, Armisen J, Miska EA, Standart N. (2009). Two Piwi proteins, Xiwi and Xili, are expressed in the Xenopus female germline. RNA 15:337-45.
4. Marnef, A., Maldonado, M., Bugaut, A., Balasubramanian, S., Kress, M., Weil, D. and Standart, N. (2010). Distinct functions of maternal and somatic Pat1 protein paralogs. RNA, 16, 2094-2107
5. Marnef A, Weil D, Standart N. (2012). RNA-related nuclear functions of human Pat1b, the P-body mRNA decay factor.
Mol Biol Cell. 23:213-24