Interactions between mRNA export commitment, 3'-end quality control, and nuclear degradation.
Several aspects of eukaryotic mRNA processing are linked to transcription. In Saccharomyces cerevisiae, overexpression of the mRNA export factor Sub2p suppresses the growth defect of hpr1 null cells, yet the protein Hpr1p and the associated THO protein complex are implicated in transcriptional elongation. Indeed, we find that a pool of heat shock HSP104 transcripts are 3'-end truncated in THO complex mutant as well as sub2 mutant backgrounds. Surprisingly, however, this defect can be suppressed by deletion of the 3'-5' exonuclease Rrp6p. This indicates that incomplete RNAs result from nuclear degradation rather than from a failure to efficiently elongate transcription. RNAs that are not degraded are retained at the transcription site in a Rrp6p-dependent manner. Interestingly, the addition of a RRP6 deletion to sub2 or to THO complex mutants shows a strong synthetic growth phenotype, suggesting that the failure to retain and/or degrade defective mRNAs is deleterious. mRNAs produced in the 3'-end processing mutants rna14-3 and rna15-2, as well as an RNA harboring a 3' end generated by a self-cleaving hammerhead ribozyme, are also retained in Rrp6p-dependent transcription site foci. Taken together, our results show that several classes of defective RNPs are subject to a quality control step that impedes release from transcription site foci and suggest that suboptimal messenger ribonucleoprotein assembly leads to RNA degradation by Rrp6p.
Libri
Domenico
D
Centre National de la Recherche Scientifique, Centre de Genetique Moleculaire, 91190 Gif-sur-Yvette, France. Libri@cgm.cnrs-gif.fr
Dower
Ken
K
Boulay
Jocelyne
J
Thomsen
Rune
R
Rosbash
Michael
M
Jensen
Torben Heick
TH
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; D005656:Fungal Proteins / Q000378:metabolism; D005800:Genes, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D026721:RNA 3' End Processing; D012333:RNA, Messenger / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D005656:Fungal Proteins; C063494:HPR1 protein, S cerevisiae; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C112610:RRP6 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C027900:RNA-dependent ATPase