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

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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. © 2006 Elsevier Inc. All rights reserved.

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Conrad, N. K., Mili, S., Marshall, E. L., Shu, M. D., & Steitz, J. A. (2006). Identification of a Rapid Mammalian Deadenylation-Dependent Decay Pathway and Its Inhibition by a Viral RNA Element. Molecular Cell, 24(6), 943–953. https://doi.org/10.1016/j.molcel.2006.10.029

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