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Published March 2007 | Supplemental Material
Journal Article Open

Contribution of Trf4/5 and the Nuclear Exosome to Genome Stability Through Regulation of Histone mRNA Levels in Saccharomyces cerevisiae


Balanced levels of histones are crucial for chromosome stability, and one major component of this control regulates histone mRNA amounts. The Saccharomyces cerevisiae poly(A) polymerases Trf4 and Trf5 are involved in a quality control mechanism that mediates polyadenylation and consequent degradation of various RNA species by the nuclear exosome. None of the known RNA targets, however, explains the fact that trf mutants have specific cell cycle defects consistent with a role in maintaining genome stability. Here, we investigate the role of Trf4/5 in regulation of histone mRNA levels. We show that loss of Trf4 and Trf5, or of Rrp6, a component of the nuclear exosome, results in elevated levels of transcripts encoding DNA replication-dependent histones. Suggesting that increased histone levels account for the phenotypes of trf mutants, we find that TRF4 shows synthetic genetic interactions with genes that negatively regulate histone levels, including RAD53. Moreover, synthetic lethality of trf4Δ rad53Δ is rescued by reducing histone levels whereas overproduction of histones is deleterious to trf's and rrp6Δ mutants. These results identify TRF4, TRF5, and RRP6 as new players in the regulation of histone mRNA levels in yeast. To our knowledge, the histone transcripts are the first mRNAs that are upregulated in Trf mutants.

Additional Information

© 2007 by the Genetics Society of America. Manuscript received September 21, 2006; Accepted for publication December 6, 2006. We thank Rochelle Diamond for assistance with flow cytometry; J. F. Diffley for the Rad53 antibody; M. Foiani for the rad53K227A strain; M. F. Christman for the CY1243 strain; and R. Rothstein for the W2017-7C, U960-5C, and U953-61A strains. We thank R. Parker for helpful discussions and for supplying the RNaseH protocol. C.C.R. is supported by a predoctoral fellowship from Fundacao para a Ciencia e Tecnologia (SFRH/BD/9612/2002), Portugal. This work was supported by National Institutes of Health grant GM25508 and by a grant from the Research Management Group.

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