title: Identification of a rapid mammalian deadenylation-dependent decay pathway and its inhibition by a viral RNA element.
abstract: Cellular RNAs are subject to quality-control pathways that insure the fidelity of gene expression. We previously identified a 79 nt element, the ENE, that is essential for the nuclear accumulation of a viral polyadenylated nuclear (PAN) RNA. Here, we show that intron-less polyadenylated transcripts such as PAN RNA and beta-globin cRNA exhibit two-component exponential decay kinetics in which some transcripts are rapidly degraded (t(1/2) = approximately 15 min) while others decay more slowly (t(1/2) = approximately 3 hr). Inclusion of the ENE protects such transcripts from rapid decay in a poly(A)-dependent fashion. The ENE inhibits deadenylation and decay in nuclear extract and prevents deadenylation of naked RNA by a purified deadenylase, likely through snoRNA-like intramolecular hybridization with the poly(A) tail. The ENE causes increased accumulation of splicing-defective beta-globin pre-mRNAs in vivo. We propose that the ENE-controlled rapid-decay mechanism for polyadenylated transcripts comprises a nuclear pre-mRNA surveillance system in mammalian cells.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06536, USA.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Conrad
authors.forename: Stavroula
authors.initials: S
authors.lastname: Mili
authors.forename: Eleanor L
authors.initials: EL
authors.lastname: Marshall
authors.forename: Mei-Di
authors.initials: MD
authors.lastname: Shu
authors.forename: Joan A
authors.initials: JA
authors.lastname: Steitz
mesh_terms: D001483:Base Sequence; D004602:Elements; D005914:Globins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D026723:Polyadenylation; D022821:RNA Splice Sites; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D004602:Elements; D022821:RNA Splice Sites; D012333:RNA, Messenger; D012367:RNA, Viral; D005914:Globins