title: Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast.
abstract: We measured half-lives of 21,248 mRNA 3' isoforms in yeast by rapidly depleting RNA polymerase II from the nucleus and performing direct RNA sequencing throughout the decay process. Interestingly, half-lives of mRNA isoforms from the same gene, including nearly identical isoforms, often vary widely. Based on clusters of isoforms with different half-lives, we identify hundreds of sequences conferring stabilization or destabilization upon mRNAs terminating downstream. One class of stabilizing element is a polyU sequence that can interact with poly(A) tails, inhibit the association of poly(A)-binding protein, and confer increased stability upon introduction into ectopic transcripts. More generally, destabilizing and stabilizing elements are linked to the propensity of the poly(A) tail to engage in double-stranded structures. Isoforms engineered to fold into 3' stem-loop structures not involving the poly(A) tail exhibit even longer half-lives. We suggest that double-stranded structures at 3' ends are a major determinant of mRNA stability.
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: Joseph V
authors: JV
authors: Geisberg
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: Zarmik
authors: Z
authors: Moqtaderi
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: Xiaochun
authors: X
authors: Fan
authors: Helicos BioSciences Corporation, 1 Kendall Square, Cambridge, MA 02139, USA.
authors: Fatih
authors: F
authors: Ozsolak
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kevin@hms.harvard.edu.
authors: Kevin
authors: K
authors: Struhl
mesh_terms: D001483:Base Sequence; D016681:Genome, Fungal; D055106:Genome-Wide Association Study; D006207:Half-Life; D059372:Nucleotide Motifs; D020871:RNA Stability; D012331:RNA, Fungal / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D012331:RNA, Fungal; D012333:RNA, Messenger