Post-transcriptional regulation by subcellular mRNA localisation

Maria (Sasi) 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

Post-transcriptional regulation constitutes a crucial step in control of information flow from genes to proteins, and is mediated by concerted action of RNA-Binding-Proteins (RBPs). Many RBPs are also involved in subcellular localisation of mRNAs. However, to what extent mRNA localisation influences post-transcriptional regulation is unclear. We have found an RBP named LARP6 to play a crucial role in regulation of RNA localisation in human mesenchymal cells. The aim of this project is to elucidate the molecular mechanisms underlying LARP6 function, clarify its role with regards to the spatial regulation of mRNAs, and ultimately understand how this affects key cellular processes such as cell proliferation, migration, and survival.
This interdisciplinary work will be conducted using integrated structural, biochemical, multi-omics, and cellular approaches.


References

Mardakheh FK*, Paul A, K├╝mper S, Sadok A, Paterson H, Mccarthy A, Yuan Y, Marshall CJ (2015) Global Analysis of mRNA, Translation, and Protein Localization: Local Translation Is a Key Regulator of Cell Protrusions. Dev Cell. 35:344-57.

Maraia, R.J.*, Mattijssen, S., Cruz-Gallardo, I., Conte, M.R.* (2017) The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives. Wiley Interdiscip Rev RNA. 8(6) doi: 10.1002/wrna.1430.

Martino, L., Pennell, S., Kelly, G., Busi, B., Brown, P., Atkinson, R.A., Salisbury, N.J.H., Ooi, Z-H., See, K-W., Smerdon, S.J., Alfano, C., Bui, T.T., Conte, M.R.* (2015) Synergic interplay of the La motif, RRM1, and the interdomain linker of LARP6 in the recognition of collagen mRNA expands the RNA binding repertoire of the La module. Nucleic Acids Res, 43, 645-60.

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., Epub, doi: 10.1093/nar/gkz144.

Dermit M, Dodel M, Mardakheh FK*. (2017) Methods for monitoring and measurement of protein translation in time and space. Mol Biosyst. 13:2477-2488.


BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyStructural Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsGeneticsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular Biology