A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities

Ghosh, Pritha; Grellscheid, Sushma Nagaraja; Sowdhamini, R.

Abstract

The Transformer2 (Tra2) proteins in humans are homologues of the Drosophila Tra2 protein. One of the two RNA-binding paralogs, Tra2β, has been very well-studied over the past decade, but not much is known about Tra2α. It was very recently shown that the two proteins demonstrate the phenomenon of paralog compensation. Here, we provide a structural basis for this genetic backup circuit, using molecular modelling and dynamics studies. We show that the two proteins display similar binding specificities, but differential affinities to a short GAA-rich RNA stretch. Starting from the 6-nucleotide RNA in the solution structure, close to 4000 virtual mutations were modelled on RNA and the domain–RNA interactions were studied after energy minimisation to convergence. Separately, another known 13-nucleotide stretch was docked and the domain–RNA interactions were observed through a 100-ns dynamics trajectory. We have also demonstrated the ‘compensatory’ mechanism at the level of domains in one of the domain repeat-containing RNA-binding proteins.

Citation

Ghosh, P., Grellscheid, S. N., & Sowdhamini, R. (2016). A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities. Journal of Biomolecular Structure and Dynamics, 34(9), 1979-1986. https://doi.org/10.1080/07391102.2015.1100551

• Journal Article Type: Article
• Acceptance Date: Sep 15, 2015
• Online Publication Date: Nov 26, 2015
• Publication Date: 2016-09
• Deposit Date: Aug 25, 2017
• Journal: Journal of Biomolecular Structure and Dynamics
• Print ISSN: 0739-1102
• Electronic ISSN: 1538-0254
• Publisher: Taylor and Francis Group
• Peer Reviewed: Peer Reviewed
• Volume: 34
• Issue: 9
• Pages: 1979-1986
• DOI: https://doi.org/10.1080/07391102.2015.1100551
• Public URL: https://durham-repository.worktribe.com/output/1377985