Atlanta Cook

Structural biology of macromolecular complexes in RNA metabolism.

Atlanta Cook holds a personal chair of structural biology of gene expression. Her group studies RNA-protein interactions and their mechanisms in controlling of gene expression using biochemical and structural approaches.

Atlanta did her PhD on mechanistic studies of protein kinases with Dame Prof. Louise Johnson in Oxford. She joined the laboratory of Elena Conti in 2004 to work on the structural basis of tRNA export at the EMBL in Heidelberg. She completed this work after moving with the Conti laboratory to the MPI for Biochemistry in Martinsried near Munich. She started her group in Edinburgh in 2011, funded by an MRC Career Development Award and was subsequently supported by a Wellcome Trust Senior Fellowship. In 2017 she was awarded an Early Career Researcher prize from the British Crystallographic Association.

portrait photo of Atlanta Cook
Atlanta Cook

Thanh Le and Sophie Winterbourne


The expression of individual genes is controlled at the levels of mRNA by processes such as splicing, RNA localization, modification or editing, and degradation. To gain a mechanistic understanding of these processes it is important to understand the interactions between protein and RNA at the molecular level. We have used structural approaches to tackle mechanistic questions about how protein-RNA interactions control RNA. By combining structural studies with biochemical, biophysical and cell-based functional assays we can gain powerful insights into these molecular processes.

Recently, we used integrative structural approaches, to characterise how a common essential human protein complex interacts with double stranded (ds) RNA. Human introns are common targets for insertion of transposable elements that can generate secondary structures within and between intronic elements. The protein complex, comprised of  nuclear factors 45 and 90 (NF45-NF90),  recognise long stretches of dsRNA and can alter both RNA splicing and editing. Using solution methods, such as small angle X-ray scattering and quantitative cross-linking mass spectrometry, along with electron microscopy, we discovered that NF45-NF90 complexes undergo architectural rearrangement of their domains on binding dsRNA that allows them to coat long stretches of dsRNA. This has important implications for regulation of post-transcriptional processing of mRNAs. 


Diagram of Protein and RNA complexes

Figure A. Characterisation of NF45-NF90 complexes using (clockwise from top left) small angle X-ray scattering to provide information on shape, cross-linking mass spectrometry for distance constraints of domains, machine learning to predict RNA binding sites and negative stain electron microscopy to reveal direct interactions with dsRNA. 

Figure B. Integrating approaches suggests a model where domain rearrangements and multiple binding events on dsRNA can lead to “coating” of dsRNA. 

Winterbourne S., Jayachandran U., Zou J., Rappsilber J., Granneman S., Cook A.G. (2025) Integrative structural analysis of NF45–NF90 heterodimers reveals architectural rearrangements and oligomerization on binding dsRNA.Nucleic Acids Research 53 (6), gkaf204; DOI: 10.1093/nar/gkaf204

Zoch A., Konieczny G., Auchynnikava T., Stallmeyer B., Rotte N., Heep M., Berrens R.V., Schito M., Kabayama Y., Schöpp T., Kliesch S., Houston B., Nagirnaja L., O’Bryan M.K., Aston K.I., Conrad D.F., Rappsilber J., Allshire R.C., Cook A.G., Tüttelmann F., O’Carroll D. (2024) C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line. Mol Cell 84:1021-1035. e11

Haque N., Will A., Cook A.G., Hogg J.R. (2023) A network of DZF proteins controls alternative splicing regulation and fidelity. Nucleic Acids Research 51:6411-6429

Bayne R.A., Jayachandran U., Kasprowicz A., Bresson S., Tollervey D., Wallace E.W.J., Cook A.G. (2021) Yeast Ssd1 is a non-enzymatic member of the RNase II family with an alternative RNA recognition interface. Nucleic Acids Research, DOI: 10.1093/nar/gkab615.

Pantier R., Chhatbar K., Quante T., Skourti-Stathaki K., Cholewa-Waclaw J., Alston G., Alexander-Howden B., Lee H.Y., Cook A.G., C Spruijt C.G., Vermeulen M., Selfridge J., and Bird A. (2021) SALL4 controls cell fate in response to DNA base composition. Mol Cell 81:845-858.e8.

Ballou E.R., Cook A.G. and Wallace E.W.J. (2020) Repeated evolution of inactive pseudonucleases in a fungal branch of the Dis3/RNase II family of nucleases. Mol. Biol. Evol. doi:10.1093/molbev/msaa324


This article was published on