Cyclin CLB2 mRNA localization and protein synthesis link cell cycle progression to bud growth

Anna Maekiniemi; Philipp Savakis; Kelly van Rossum; Jacky L. Snoep; Markus Seiler; David D. van Niekerk; Kathi Zarnack; Robert H. Singer; Evelina Tutucci

doi:10.1038/s41467-025-66623-w

Cyclin CLB2 mRNA localization and protein synthesis link cell cycle progression to bud growth

Anna Maekiniemi
, Philipp Savakis
, Kelly van Rossum
, Jacky L. Snoep
, Markus Seiler
, David D. van Niekerk
, Kathi Zarnack
, Robert H. Singer
, Evelina Tutucci^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Clb2 is a conserved B-type cyclin essential for mitotic progression in Saccharomyces cerevisiae, with expression tightly regulated at transcriptional and proteolytic levels. However, it remains unclear whether Clb2 protein synthesis is regulated and responsive to cell growth. Here, we show that CLB2 mRNA localizes to the bud via the She2/She3 complex, while Clb2 protein accumulates in the mother nucleus. This mRNA localization enhances translation without affecting protein localization. A structured RNA element, a ZIP-code, is located within the coding sequence and is required, but not sufficient, for both mRNA transport and protein expression. Mutation of this ZIP code disrupts mRNA localization, reduces Clb2 synthesis, increases budded phase duration and daughter cell size. In wild-type cells, Clb2 protein levels scale with bud growth, a coupling lost in ZIP code mutants. These findings reveal a mechanism by which mRNA localization and translation are coordinated to link cell growth with cell cycle progression.

Original language	English
Article number	11654
Pages (from-to)	1-19
Number of pages	19
Journal	Nature Communications
Volume	16
Issue number	1
Early online date	30 Dec 2025
DOIs	https://doi.org/10.1038/s41467-025-66623-w
Publication status	Published - Dec 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

This work was supported by NIH grant GM57071 to R.H.S. E.T. was supported by Swiss National Science Foundation Fellowships P2GEP3_155692 and P300PA_164717, as well as by the Vrije Universiteit Amsterdam. We acknowledge financial support from the Department of Science and Technology/National Research Foundation in South Africa (grant NRF-SARCHI-82813 to J.L.S.) and grant 116298 (to D.D.v.N.). K.Z. was supported by the Deutsche Forschungsgemeinschaft (DFG) via the Research Unit FOR2333 (ZA 881/3-1). We thank X. Meng for help with cloning. J. Wiemerink for help with flow cytometry. M. Collart (CMU, Geneva) for the RPT2 smFISH probes. A. Gerber for discussion and critical reading of the manuscript, W. Li, C. Eliscovich, F. Bruggeman, S. Das and all the members of the lab for discussion.

Funders	Funder number
CMU
Department of Science and Technology, Republic of South Africa
National Research Foundation	116298, NRF-SARCHI-82813
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	P300PA_164717, P2GEP3_155692
National Institutes of Health	GM57071
Deutsche Forschungsgemeinschaft	ZA 881/3-1

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title = "Cyclin CLB2 mRNA localization and protein synthesis link cell cycle progression to bud growth",

abstract = "Clb2 is a conserved B-type cyclin essential for mitotic progression in Saccharomyces cerevisiae, with expression tightly regulated at transcriptional and proteolytic levels. However, it remains unclear whether Clb2 protein synthesis is regulated and responsive to cell growth. Here, we show that CLB2 mRNA localizes to the bud via the She2/She3 complex, while Clb2 protein accumulates in the mother nucleus. This mRNA localization enhances translation without affecting protein localization. A structured RNA element, a ZIP-code, is located within the coding sequence and is required, but not sufficient, for both mRNA transport and protein expression. Mutation of this ZIP code disrupts mRNA localization, reduces Clb2 synthesis, increases budded phase duration and daughter cell size. In wild-type cells, Clb2 protein levels scale with bud growth, a coupling lost in ZIP code mutants. These findings reveal a mechanism by which mRNA localization and translation are coordinated to link cell growth with cell cycle progression.",

author = "Anna Maekiniemi and Philipp Savakis and \{van Rossum\}, Kelly and Snoep, \{Jacky L.\} and Markus Seiler and \{van Niekerk\}, \{David D.\} and Kathi Zarnack and Singer, \{Robert H.\} and Evelina Tutucci",

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AU - Maekiniemi, Anna

AU - Savakis, Philipp

AU - van Rossum, Kelly

AU - Snoep, Jacky L.

AU - Seiler, Markus

AU - van Niekerk, David D.

AU - Zarnack, Kathi

AU - Singer, Robert H.

AU - Tutucci, Evelina

PY - 2025/12

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N2 - Clb2 is a conserved B-type cyclin essential for mitotic progression in Saccharomyces cerevisiae, with expression tightly regulated at transcriptional and proteolytic levels. However, it remains unclear whether Clb2 protein synthesis is regulated and responsive to cell growth. Here, we show that CLB2 mRNA localizes to the bud via the She2/She3 complex, while Clb2 protein accumulates in the mother nucleus. This mRNA localization enhances translation without affecting protein localization. A structured RNA element, a ZIP-code, is located within the coding sequence and is required, but not sufficient, for both mRNA transport and protein expression. Mutation of this ZIP code disrupts mRNA localization, reduces Clb2 synthesis, increases budded phase duration and daughter cell size. In wild-type cells, Clb2 protein levels scale with bud growth, a coupling lost in ZIP code mutants. These findings reveal a mechanism by which mRNA localization and translation are coordinated to link cell growth with cell cycle progression.

AB - Clb2 is a conserved B-type cyclin essential for mitotic progression in Saccharomyces cerevisiae, with expression tightly regulated at transcriptional and proteolytic levels. However, it remains unclear whether Clb2 protein synthesis is regulated and responsive to cell growth. Here, we show that CLB2 mRNA localizes to the bud via the She2/She3 complex, while Clb2 protein accumulates in the mother nucleus. This mRNA localization enhances translation without affecting protein localization. A structured RNA element, a ZIP-code, is located within the coding sequence and is required, but not sufficient, for both mRNA transport and protein expression. Mutation of this ZIP code disrupts mRNA localization, reduces Clb2 synthesis, increases budded phase duration and daughter cell size. In wild-type cells, Clb2 protein levels scale with bud growth, a coupling lost in ZIP code mutants. These findings reveal a mechanism by which mRNA localization and translation are coordinated to link cell growth with cell cycle progression.

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Cyclin CLB2 mRNA localization and protein synthesis link cell cycle progression to bud growth

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