The role of La and Related Protein family in ribosome biogenesis

Maria R Conte (primary)
Randall Centre for Cell and Molecular Biophysics
King's College London
Faraz Mardakheh (secondary)
Barts Cancer Institute
Queen Mary University of London

Abstract

The La-related protein – LARP- superfamily constitute an evolutionary conserved group of RNA Binding Proteins – RBPs. Humans contain seven LARP paralogues, a number of which have been shown to control ribosome biogenesis, a central process in every living cell. It is however unclear whether this is a conserved feature of all LARPs and the extent of their functional and mechanistic overlap remains to be understood. The aim of this project is to systematically assess the impact of each human LARP paralogue towards regulation of ribosome biogenesis, as well as revealing the molecular mechanisms of this regulation.
This interdisciplinary work will be conducted using integrated structural, biochemical, multi-omics, and cellular approaches, taking advantage of the complementary expertise of the two supervisors.


References

1. Maraia, R.J.*, Mattijssen, S., Cruz-Gallardo, I., Conte, M.R.* 2017. The La and related RNA-binding proteins: structures, functions, and evolving perspectives. Wiley Interdiscip Rev RNA. 8 doi: 10.1002/wrna.1430.
2. Dermit M , Dodel M , Lee FCY, Azman MS , Schwenzer H, Jones JL, Blagden SP, Ule J, Mardakheh FK* 2019. Subcellular mRNA localization regulates ribosome biogenesis in migrating cells. Developmental Cell 35, 3, 298-313.
3. Dermit M, Dodel M, Mardakheh FK*. 2017. Methods for monitoring and measurement of protein translation in time and space. Mol Biosyst. 13:2477-2488.
4. Cruz-Gallardo, I., Martino, L., Kelly, G., Atkinson, A., Trotta, R., De Tito, S., Coleman, P., Ahdash, Z., Gu, Y., Bui, T.TT Conte, M.R.* 2019. LARP4A recognises polyA RNA via a novel binding mechanism mediated by disordered regions and involving the PAM2w motif, revealing interplay between PABP, LARP4A and mRNA. Nucleic Acids Res., 47:4272-4291. doi: 10.1093/nar/gkz144.
5. Lizarrondo, J., Dock-Bregeon, A.C., Martino, L.* and Conte, M.R.* 2021. Structural dynamics in the La-module of La-related proteins. RNA biology, 18:194-206. doi: 10.1080/15476286.2020.1733799.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyStructural Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsGeneticsMathematics / StatisticsMolecular Biology