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Sequence, structural and functional conservation among the human and fission yeast ELL and EAF transcription elongation factors

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Abstract

Background

Transcription elongation is a dynamic and tightly regulated step of gene expression in eukaryotic cells. Eleven nineteen Lysine rich Leukemia (ELL) and ELL Associated Factors (EAF) family of conserved proteins are required for efficient RNA polymerase II-mediated transcription elongation. Orthologs of these proteins have been identified in different organisms, including fission yeast and humans.

Methods and Results

In the present study, we have examined the sequence, structural and functional conservation between the fission yeast and human ELL and EAF orthologs. Our computational analysis revealed that these proteins share some sequence characteristics, and were predominantly disordered in both organisms. Our functional complementation assays revealed that both human ELL and EAF proteins could complement the lack of ell1+ or eaf1+ in Schizosaccharomyces pombe respectively. Furthermore, our domain mapping experiments demonstrated that both the amino and carboxyl terminal domains of human EAF proteins could functionally complement the S. pombe eaf1 deletion phenotypes. However, only the carboxyl-terminus domain of human ELL was able to partially rescue the phenotypes associated with lack of ell1+ in S. pombe.

Conclusions

Collectively, our work adds ELL-EAF to the increasing list of human-yeast complementation gene pairs, wherein the simpler fission yeast can be used to further enhance our understanding of the role of these proteins in transcription elongation and human disease.

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Acknowledgements

The authors thank Prof. Susan Forsburg (University of Southern California, USA), Prof. Richard Maraia (National Institutes of Health, USA), Dr. Joan Conaway (Stowers Institute for Medical Research, USA) and Prof. Antony Carr (University of Sussex, UK) for kindly providing yeast strains and plasmids used in this work. The authors would also like to thank Dr Swati Tiwari (Jawaharlal Nehru University, India) for the generous gift of anti-HA antibody. This work was funded by a grant from the Department of Biotechnology, Govt. of India (Grant No. BT/PR12568/BRB/10/1369/2015). P.D was supported by a fellowship from University Grants Commission, Government of India and Guru Gobind Singh Indraprastha University (STRF).

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  1. Kumari Sweta and Preeti Dabas have equally contributed to this work.

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  1. University School of Biotechnology, G.G.S. Indraprastha University, Sector 16C, Dwarka, New Delhi, 110078, India

    Kumari Sweta, Preeti Dabas & Nimisha Sharma

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  1. Kumari Sweta
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KS and PD performed all experiments. KS, PD and NS contributed in designing the experiments, analyzing and interpreting the data. All authors were involved in writing the manuscript. NS conceptualized the study and procured funding for this work.

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Correspondence to Nimisha Sharma.

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Sweta, K., Dabas, P. & Sharma, N. Sequence, structural and functional conservation among the human and fission yeast ELL and EAF transcription elongation factors. Mol Biol Rep 49, 1303–1320 (2022). https://doi.org/10.1007/s11033-021-06958-x

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