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

doi:10.1016/j.molcel.2006.10.029

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

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89 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 (t_1/2 = ∼15 min) while others decay more slowly (t_1/2 = ∼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 language	English (US)
Pages (from-to)	943-953
Number of pages	11
Journal	Molecular cell
Volume	24
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2006.10.029
State	Published - Dec 28 2006

Keywords

RNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2006.10.029

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@article{ea97c58586414b5ebc5f46bfd9952a88,

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 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.",

keywords = "RNA",

author = "Conrad, {Nicholas K.} and Stavroula Mili and Marshall, {Eleanor L.} and Shu, {Mei Di} and Steitz, {Joan A.}",

note = "Funding Information: We thank Jens Lykke-Andersen (University of Colorado), Elmar Wahle (University of Halle), and Ann-Bin Shyu (University of Texas) for providing reagents, and Drs. Ian Macara (University of Virginia), Shobha Vasudevan, Kazimierz Tycowski, and Andrei Alexandrov for critical review of the manuscript. We thank Dr. Roy Parker for helpful insights into the interpretation of our data, and Dr. Konstadinos Moissoglu and Nikos Milis for advice regarding data analysis. This work was supported by National Institutes of Health (NIH) grant CA16038. J.A.S. is an investigator of the Howard Hughes Medical Institute. N.K.C. was a fellow of the Damon Runyon Cancer Research Foundation (DRG#1722-02) and is currently supported by NIH grant T32-CA09159-29. S.M. is a fellow of the Leukemia and Lymphoma Society, and E.L.M. was supported by the Arnold and Mabel Beckman Foundation. ",

year = "2006",

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doi = "10.1016/j.molcel.2006.10.029",

language = "English (US)",

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T1 - Identification of a Rapid Mammalian Deadenylation-Dependent Decay Pathway and Its Inhibition by a Viral RNA Element

AU - Conrad, Nicholas K.

AU - Mili, Stavroula

AU - Marshall, Eleanor L.

AU - Shu, Mei Di

AU - Steitz, Joan A.

N1 - Funding Information: We thank Jens Lykke-Andersen (University of Colorado), Elmar Wahle (University of Halle), and Ann-Bin Shyu (University of Texas) for providing reagents, and Drs. Ian Macara (University of Virginia), Shobha Vasudevan, Kazimierz Tycowski, and Andrei Alexandrov for critical review of the manuscript. We thank Dr. Roy Parker for helpful insights into the interpretation of our data, and Dr. Konstadinos Moissoglu and Nikos Milis for advice regarding data analysis. This work was supported by National Institutes of Health (NIH) grant CA16038. J.A.S. is an investigator of the Howard Hughes Medical Institute. N.K.C. was a fellow of the Damon Runyon Cancer Research Foundation (DRG#1722-02) and is currently supported by NIH grant T32-CA09159-29. S.M. is a fellow of the Leukemia and Lymphoma Society, and E.L.M. was supported by the Arnold and Mabel Beckman Foundation.

PY - 2006/12/28

Y1 - 2006/12/28

N2 - 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.

AB - 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.

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VL - 24

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JO - Molecular cell

JF - Molecular cell

IS - 6

ER -

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

Abstract

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