Originally published as Genetics Published Articles Ahead of Print on December 18, 2006.

Genetics, Vol. 175, 993-1010, March 2007, Copyright © 2007
doi:10.1534/genetics.106.065987

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

* Braun Laboratories, California Institute of Technology, Pasadena, California 91125 and {dagger} Gulbenkian Ph.D. Program in Biomedicine, Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal

1 Corresponding author: Braun Laboratories, 147-75, California Institute of Technology, Pasadena, CA 91125.
E-mail: jcampbel{at}caltech.edu

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 trf4{Delta} rad53{Delta} is rescued by reducing histone levels whereas overproduction of histones is deleterious to trf's and rrp6{Delta} 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.




This article has been cited by other articles:


Home page
Mol. Biol. CellHome page
A. C. Graham, D. L. Kiss, and E. D. Andrulis
Core Exosome-independent Roles for Rrp6 in Cell Cycle Progression
Mol. Biol. Cell, April 15, 2009; 20(8): 2242 - 2253.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
R. Nakamura, R. Takeuchi, K.-i. Takata, K. Shimanouchi, Y. Abe, Y. Kanai, T. Ruike, A. Ihara, and K. Sakaguchi
TRF4 Is Involved in Polyadenylation of snRNAs in Drosophila melanogaster
Mol. Cell. Biol., November 1, 2008; 28(21): 6620 - 6631.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M. Jaszczur, K. Flis, J. Rudzka, J. Kraszewska, M. E. Budd, P. Polaczek, J. L. Campbell, P. Jonczyk, and I. J. Fijalkowska
Dpb2p, a Noncatalytic Subunit of DNA Polymerase {varepsilon}, Contributes to the Fidelity of DNA Replication in Saccharomyces cerevisiae
Genetics, February 1, 2008; 178(2): 633 - 647.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
C. J. Wilusz and J. Wilusz
New ways to meet your (3') end oligouridylation as a step on the path to destruction
Genes & Dev., January 1, 2008; 22(1): 1 - 7.
[Full Text] [PDF]


Home page
Nucleic Acids ResHome page
H. A. Meijer, M. Bushell, K. Hill, T. W. Gant, A. E. Willis, P. Jones, and C. H. de Moor
A novel method for poly(A) fractionation reveals a large population of mRNAs with a short poly(A) tail in mammalian cells
Nucleic Acids Res., October 11, 2007; (2007) gkm830v1.
[Abstract] [Full Text] [PDF]