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PMID: 17179095 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Contribution of Trf4/5 and the nuclear exosome to genome stability through regulation of histone mRNA levels in Saccharomyces cerevisiae.

Genetics ·Vol. 175 ·No. 3 ·2007-03-00 ·Pages 993-1010

Reis CC, Campbell JL

Abstract

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 trf4Delta rad53Delta is rescued by reducing histone levels whereas overproduction of histones is deleterious to trf's and rrp6Delta 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.

MeSH Terms
Blotting, Northern DNA-Directed DNA Polymerase/genetics DNA-Directed RNA Polymerases/genetics Exoribonucleases/genetics Exosome Multienzyme Ribonuclease Complex Flow Cytometry Gene Expression Regulation, Fungal/genetics Genomic Instability/genetics Histones/genetics,metabolism Oligonucleotides/genetics RNA, Messenger/metabolism Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/genetics
Chemicals
Histones Oligonucleotides RNA, Messenger Saccharomyces cerevisiae Proteins DNA-Directed RNA Polymerases Trf5 protein, S cerevisiae DNA-Directed DNA Polymerase PAP2 protein, S cerevisiae Exoribonucleases Exosome Multienzyme Ribonuclease Complex RRP6 protein, S cerevisiae
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Reis Clara C
Braun Laboratories, California Institute of Technology, Pasadena, California 91125, USA.
Campbell Judith L
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1534/genetics.106.065987
Published
2007-03-00
Epub
2006-00-18
Pages
993-1010
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1840065
Subset
IM
Grants
NIGMS NIH HHS · R01 GM025508 · United States
NIGMS NIH HHS · GM25508 · United States
External Links
PubMed source DOI: 10.1534/genetics.106.065987 PMC Full Text View journal details
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