Identification of a Rapid Mammalian Deadenylation-Dependent Decay Pathway and Its Inhibition by a Viral RNA Element

Nicholas K. Conrad, Stavroula Mili, Eleanor L. Marshall, Mei Di Shu, Joan A. Steitz

Research output: Contribution to journalArticle

73 Scopus citations

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 β-globin cRNA exhibit two-component exponential decay kinetics in which some transcripts are rapidly degraded (t1/2 = ∼15 min) while others decay more slowly (t1/2 = ∼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 β-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.

Original languageEnglish (US)
Pages (from-to)943-953
Number of pages11
JournalMolecular Cell
Volume24
Issue number6
DOIs
Publication statusPublished - Dec 28 2006

    Fingerprint

Keywords

  • RNA

ASJC Scopus subject areas

  • Molecular Biology

Cite this