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doi:10.1534/genetics.106.065987
A more recent version of this article appeared on March 1, 2007.
REGULAR RESEARCH PAPERS |
Contribution of Trf4/5 and the nuclear exosome to genome stability through regulation of histone mRNA levels in Saccharomyces cerevisiae
Clara C. Reis 1 and Judith L. Campbell 2*
1 Instituto Gulbenkian de Ciência
2 California Institute of Technology
* To whom correspondence should be addressed. E-mail: jcampbel{at}its.caltech.edu.
Submitted on September 21, 2006
Revised on November 2, 2006
Accepted on 6 December 2006
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 trf4D rad53D is rescued by reducing histone levels whereas overproduction of histones is deleterious to trfs and rrp6D 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.
Key Words: Cell cycle, Chromatin, Genome stability, Transcription, Yeast
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