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Translational regulation of δ-tubulin through its 5’-untranslated region

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Abstract

Background

δ-tubulin - a member of tubulin superfamily, is found in a subset of eukaryotes including human where it has a role in centriole maturation. The mutation in the gene results in a disorganized microtubule triplet arrangement leading to formation of defective centriole. Since centriole maturation is a periodic event, it will be interesting to see if δ-tubulin is also regulated in a cell cycle dependent manner.

Methods and results

In this regard we show that the abundance of δ-tubulin mRNA remains unchanged throughout the cell cycle. However, the protein level varies periodically with a significantly higher expression in S-phase, implying regulation at the level of translation. Sequence analysis establishes the presence of a 90-base long conserved region, including a consensus motif of nine residues in the 5´-untranslated region (5´-UTR) of δ-tubulin transcript. The deletion analysis of the conserved region using luciferase reporter assay system confirms its strong inhibitory effect on translation. Interestingly, microtubule associated protein 4 (MAP4) is found to interact specifically with the 90-base long conserved region in the 5´-UTR and possibly responsible, at least partially, for the translation inhibitory activity of the UTR. Remarkably, MAP4 interacts with δ-tubulin in a periodic manner at protein level also.

Conclusion

The results reported here show that δ-tubulin protein expression is regulated at posttranscriptional level and strongly suggest the role of MAP4 in modulation of both abundance and function of δ-tubulin.

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Funding

The study was supported by intramural project fund from Department of Atomic Energy, Government of India (Project Identification Code: VS8/SIN/414-RSI 4002). Fellowship to P.S.S. was provided by University Grant Commission, Government of India and that to K.S. by Saha Institute of Nuclear Physics, Kolkata, India.

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Author notes

  1. Kasturi Sengupta

    Present address: Code Biotherapeutics, 2801 Sterling Drive, PA 19440, Hatfield, USA

Authors and Affiliations

  1. Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India

    Priyadarshani Suchismita Sethy, Kasturi Sengupta, Saikat Mukhopadhyay & Partha Saha

  2. Homi Bhabha National Institute, Mumbai, India

    Priyadarshani Suchismita Sethy & Partha Saha

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  1. Priyadarshani Suchismita Sethy
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Contributions

Conceptualization: P.S.S., K.S. and P.S.; methodology and investigation: P.S.S., K.S. and S.M.; data analysis: P.S.S., K.S., S.M. and P.S.; writing, review and editing: P.S.S., K.S. and P.S.; Supervision: P.S.

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Correspondence to Partha Saha.

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Sethy, P.S., Sengupta, K., Mukhopadhyay, S. et al. Translational regulation of δ-tubulin through its 5’-untranslated region. Mol Biol Rep 50, 3451–3458 (2023). https://doi.org/10.1007/s11033-023-08289-5

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