Exonucleolysis is required for nuclear mRNA quality control in yeast THO mutants

TY - JOUR

T1 - Exonucleolysis is required for nuclear mRNA quality control in yeast THO mutants

AU - Assenholt, Jannie

AU - Mouaikel, John

AU - Andersen, Kasper Røjkjær

AU - Brodersen, Ditlev E

AU - Libri, Domenico

AU - Jensen, Torben Heick

PY - 2008/11

Y1 - 2008/11

N2 - Production of aberrant messenger ribonucleoprotein particles (mRNPs) is subject to quality control (QC). In yeast strains carrying mutations of the THO complex, transcription induction triggers a number of interconnected QC phenotypes: (1) rapid degradation of several mRNAs; (2) retention of a fraction of THO-dependent mRNAs in transcription site-associated foci; and (3) formation of a high molecular weight DNA/protein complex in the 3'-ends of THO target genes. Here, we demonstrate that the 3'-5' exonucleolytic domain of the nuclear exosome factor Rrp6p is necessary for establishing all QC phenotypes associated with THO mutations. The N terminus of Rrp6p is also important presumably through its binding to the Rrp6p co-factor Rrp47p. Interestingly, the 3'-5' exonucleolytic activity of Dis3p, the only other active exonuclease of the nuclear exosome, can also contribute to RNA QC in THO mutants, while other nuclear 3'-5' exonucleases cannot. Our data show that exonucleolytic attack by the nuclear exosome is needed both for provoking mRNP QC and for its ensuing elimination of faulty RNA.

AB - Production of aberrant messenger ribonucleoprotein particles (mRNPs) is subject to quality control (QC). In yeast strains carrying mutations of the THO complex, transcription induction triggers a number of interconnected QC phenotypes: (1) rapid degradation of several mRNAs; (2) retention of a fraction of THO-dependent mRNAs in transcription site-associated foci; and (3) formation of a high molecular weight DNA/protein complex in the 3'-ends of THO target genes. Here, we demonstrate that the 3'-5' exonucleolytic domain of the nuclear exosome factor Rrp6p is necessary for establishing all QC phenotypes associated with THO mutations. The N terminus of Rrp6p is also important presumably through its binding to the Rrp6p co-factor Rrp47p. Interestingly, the 3'-5' exonucleolytic activity of Dis3p, the only other active exonuclease of the nuclear exosome, can also contribute to RNA QC in THO mutants, while other nuclear 3'-5' exonucleases cannot. Our data show that exonucleolytic attack by the nuclear exosome is needed both for provoking mRNP QC and for its ensuing elimination of faulty RNA.

KW - DNA-Binding Proteins

KW - Exoribonucleases

KW - Exosome Multienzyme Ribonuclease Complex

KW - Fungal Proteins

KW - Nuclear Proteins

KW - Protein Structure, Tertiary

KW - RNA Processing, Post-Transcriptional

KW - RNA, Fungal

KW - RNA, Messenger

KW - RNA-Binding Proteins

KW - Ribonucleoproteins

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins

KW - Sequence Deletion

U2 - 10.1261/rna.1108008

DO - 10.1261/rna.1108008

M3 - Journal article

C2 - 18824516

SN - 1355-8382

VL - 14

SP - 2305

EP - 2313

JO - RNA

JF - RNA

IS - 11

ER -