title: YRA1 autoregulation requires nuclear export and cytoplasmic Edc3p-mediated degradation of its pre-mRNA.
abstract: Autoregulatory loops often provide precise control of the level of expression of specific genes that encode key regulatory proteins. Here we have defined a pathway by which Yra1p, a yeast mRNA export factor, controls its own expression. We show that YRA1 exon 1 sequences in cis and Yra1p in trans inhibit YRA1 pre-mRNA splicing and commit the pre-mRNA to nuclear export. Mex67p and Crm1p jointly promote YRA1 pre-mRNA export, and once in the cytoplasm, the pre-mRNA is degraded by a 5' to 3' decay mechanism that is dependent on the decapping activator Edc3p and on specific sequences in the YRA1 intron. These results illustrate how common steps in the nuclear processing, export, and degradation of a transcript can be uniquely combined to control the expression of a specific gene and suggest that Edc3p-mediated decay may have additional regulatory functions in eukaryotic cells.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Dong
authors.forename: Chunfang
authors.initials: C
authors.lastname: Li
authors.forename: Daniel
authors.initials: D
authors.lastname: Zenklusen
authors.forename: Robert H
authors.initials: RH
authors.lastname: Singer
authors.forename: Allan
authors.initials: A
authors.lastname: Jacobson
authors.forename: Feng
authors.initials: F
authors.lastname: He
mesh_terms: D021581:Active Transport, Cell Nucleus; D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D025461:Feedback, Physiological; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D028884:Karyopherins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D012315:RNA Caps / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics; D020871:RNA Stability; D034443:RNA Transport; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012261:Ribonucleoproteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012315:RNA Caps; D012322:RNA Precursors; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; D000097606:Exportin 1 Protein; C488957:EDC3 protein, S cerevisiae; C106898:MEX67 protein, S cerevisiae; C105887:YRA1 protein, S cerevisiae