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Yeast centrin Cdc31 is linked to the nuclear mRNA export machinery

Abstract

Centrins are calmodulin-like proteins that function in the duplication of microtubule-organizing centres. Here we describe a new function of the yeast centrin Cdc31. We show that overproduction of a sequence, termed CID, in the carboxy-terminal domain of the nuclear export factor Sac3 titrates Cdc31, causing a dominant-lethal phenotype and a block in spindle pole body (SPB) duplication. Under normal conditions, the CID motif recruits Cdc31 and Sus1 (a subunit of the SAGA transcription complex) to the Sac3–Thp1 complex, which functions in mRNA export together with specific nucleoporins at the nuclear basket. A previously reported cdc31 temperature-sensitive allele, which is neither defective in SPB duplication nor Kic1 kinase activation, induces mRNA export defects. Thus, Cdc31 has an unexpected link to the mRNA export machinery.

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Figure 1: Overexpression of the Sac3 CID motif produces a dominant-negative phenotype.
Figure 2: Overexpressed Sac3CID recruits Cdc31.
Figure 3: Overexpressed Sac3CID causes cell-cycle defects that can be rescued by high copy CDC31.
Figure 4: Cdc31 is a component of the Sac3–Thp1–Sus1 complex.
Figure 5: Cdc31 associates with the nuclear envelope and cdc31 mutants accumulate poly(A)+ RNA inside the nucleus.
Figure 6: Deletion of the CID motif from Sac3 causes mRNA export defects and release from the nuclear pores.
Figure 7: The CID motif of Sac3 is necessary to recruit Cdc31 and Sus1 to Sac3–Thp1.

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Acknowledgements

We would like to thank the following for technical assistance: E.-M. Lammer, M. Schneider and S. Brettschneider in the Hurt laboratory and S. Merker and P. Ihrig in the Lechner laboratory (Mass Spectrometry Unit, BZH, Heidelberg). E.C.H. was supported by grants from the Deutsche Forschungsgemeinschaft (SFB638, Leibniz-Programm) and Fonds der Chemischen Industrie.

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Correspondence to Ed Hurt.

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Fischer, T., Rodríguez-Navarro, S., Pereira, G. et al. Yeast centrin Cdc31 is linked to the nuclear mRNA export machinery. Nat Cell Biol 6, 840–848 (2004). https://doi.org/10.1038/ncb1163

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