Human Proline-Rich Nuclear Receptor Coregulatory Protein 2 Mediates an Interaction between mRNA Surveillance Machinery and Decapping Complex

Hana Cho; Kyoung Mi Kim; Yoon Ki Kim

doi:10.1016/j.molcel.2008.11.022

Human Proline-Rich Nuclear Receptor Coregulatory Protein 2 Mediates an Interaction between mRNA Surveillance Machinery and Decapping Complex

Hana Cho, Kyoung Mi Kim, Yoon Ki Kim

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132 Citations (Scopus)

Abstract

Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism by which aberrant mRNAs harboring premature termination codons are degraded before translation. However, to date, how NMD machinery recruits the general decay complex to faulty mRNAs and degrades those mRNAs remains unclear. Here we identify human proline-rich nuclear receptor coregulatory protein 2 (PNRC2) as a Upf1- and Dcp1a-interacting protein. Downregulation of PNRC2 abrogates NMD, and artificially tethering PNRC2 downstream of a normal termination codon reduces mRNA abundance. Accordingly, PNRC2 preferentially interacts with hyperphosphorylated Upf1 compared with wild-type Upf1 and triggers movement of hyperphosphorylated Upf1 into processing bodies (P bodies). Our observations suggest that PNRC2 plays an essential role in mammalian NMD, mediating the interaction between the NMD machinery and the decapping complex, so as to target the aberrant mRNA-containing RNPs into P bodies.

Original language	English
Pages (from-to)	75-86
Number of pages	12
Journal	Molecular Cell
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2008.11.022
Publication status	Published - 2009 Jan 16

Bibliographical note

Funding Information:
We thank Lynne E. Maquat for providing NMD reporter plasmids and α-Upfs antibodies; Haiwei Song for pGEX-6p-1-Upf1(295-914); Jens Lykke-Andersen for plasmids for tethering experiments, plasmids expressing FLAG-Dcp1a and Myc-HA-Rck/p54, and α-Dcp1a antibody; Sung Key Jang for yeast two-hybrid plasmids; and Hyun Kyu Song for advice on protein purification. This work was supported by a grant (20070301034003) from BioGreen 21 Program, Rural Development Administration, Republic of Korea, a grant of Seoul R&BD Program (NT070112), and a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (0820090). Kyoung Mi Kim was supported in part by Seoul Science Fellowship.

Keywords

RNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2008.11.022

Cite this

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title = "Human Proline-Rich Nuclear Receptor Coregulatory Protein 2 Mediates an Interaction between mRNA Surveillance Machinery and Decapping Complex",

abstract = "Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism by which aberrant mRNAs harboring premature termination codons are degraded before translation. However, to date, how NMD machinery recruits the general decay complex to faulty mRNAs and degrades those mRNAs remains unclear. Here we identify human proline-rich nuclear receptor coregulatory protein 2 (PNRC2) as a Upf1- and Dcp1a-interacting protein. Downregulation of PNRC2 abrogates NMD, and artificially tethering PNRC2 downstream of a normal termination codon reduces mRNA abundance. Accordingly, PNRC2 preferentially interacts with hyperphosphorylated Upf1 compared with wild-type Upf1 and triggers movement of hyperphosphorylated Upf1 into processing bodies (P bodies). Our observations suggest that PNRC2 plays an essential role in mammalian NMD, mediating the interaction between the NMD machinery and the decapping complex, so as to target the aberrant mRNA-containing RNPs into P bodies.",

keywords = "RNA",

author = "Hana Cho and Kim, {Kyoung Mi} and Kim, {Yoon Ki}",

note = "Funding Information: We thank Lynne E. Maquat for providing NMD reporter plasmids and α-Upfs antibodies; Haiwei Song for pGEX-6p-1-Upf1(295-914); Jens Lykke-Andersen for plasmids for tethering experiments, plasmids expressing FLAG-Dcp1a and Myc-HA-Rck/p54, and α-Dcp1a antibody; Sung Key Jang for yeast two-hybrid plasmids; and Hyun Kyu Song for advice on protein purification. This work was supported by a grant (20070301034003) from BioGreen 21 Program, Rural Development Administration, Republic of Korea, a grant of Seoul R&BD Program (NT070112), and a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (0820090). Kyoung Mi Kim was supported in part by Seoul Science Fellowship. ",

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AU - Kim, Yoon Ki

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PY - 2009/1/16

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N2 - Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism by which aberrant mRNAs harboring premature termination codons are degraded before translation. However, to date, how NMD machinery recruits the general decay complex to faulty mRNAs and degrades those mRNAs remains unclear. Here we identify human proline-rich nuclear receptor coregulatory protein 2 (PNRC2) as a Upf1- and Dcp1a-interacting protein. Downregulation of PNRC2 abrogates NMD, and artificially tethering PNRC2 downstream of a normal termination codon reduces mRNA abundance. Accordingly, PNRC2 preferentially interacts with hyperphosphorylated Upf1 compared with wild-type Upf1 and triggers movement of hyperphosphorylated Upf1 into processing bodies (P bodies). Our observations suggest that PNRC2 plays an essential role in mammalian NMD, mediating the interaction between the NMD machinery and the decapping complex, so as to target the aberrant mRNA-containing RNPs into P bodies.

AB - Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism by which aberrant mRNAs harboring premature termination codons are degraded before translation. However, to date, how NMD machinery recruits the general decay complex to faulty mRNAs and degrades those mRNAs remains unclear. Here we identify human proline-rich nuclear receptor coregulatory protein 2 (PNRC2) as a Upf1- and Dcp1a-interacting protein. Downregulation of PNRC2 abrogates NMD, and artificially tethering PNRC2 downstream of a normal termination codon reduces mRNA abundance. Accordingly, PNRC2 preferentially interacts with hyperphosphorylated Upf1 compared with wild-type Upf1 and triggers movement of hyperphosphorylated Upf1 into processing bodies (P bodies). Our observations suggest that PNRC2 plays an essential role in mammalian NMD, mediating the interaction between the NMD machinery and the decapping complex, so as to target the aberrant mRNA-containing RNPs into P bodies.

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Human Proline-Rich Nuclear Receptor Coregulatory Protein 2 Mediates an Interaction between mRNA Surveillance Machinery and Decapping Complex

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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