SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay

Hana Cho; Sisu Han; Ok Hyun Park; Yoon Ki Kim

doi:10.1016/j.bbagrm.2013.10.004

SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay

Hana Cho, Sisu Han, Ok Hyun Park, Yoon Ki Kim

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Suppressor of morphogenesis in genitalia 1 (SMG1), a member of the phosphatidylinositol 3-kinase-related kinase family, is involved in nonsense-mediated mRNA decay (NMD). SMG1 phosphorylates Upf1, a key NMD factor. Subsequently, hyperphosphorylated Upf1 associates with SMG5-7 or proline-rich nuclear receptor coregulatory protein (PNRC2) to elicit rapid mRNA degradation. Upf1 is also known to be involved in staufen 1 (Stau1)-mediated mRNA decay (SMD), which is closely related to NMD. However, the biological and molecular roles of SMG1 in SMD remain unknown. Here, we provide evidence that SMG1 is involved in SMD. The immunoprecipitation results show that SMG1 is complexed with Stau1, Upf1, and Dcp1a. Downregulation of SMG1 or overexpression of a kinase-inactive mutant of SMG1 inhibits SMD efficiency. In addition, downregulation of SMG1 inhibits rapid degradation elicited by artificially tethered Stau1 or Upf1 downstream of the normal termination codon. Furthermore, Stau1 and Upf1 colocalize in processing bodies in an SMG1-dependent manner. We also find that the level of SMG1 increases during adipogenesis. Accordingly, downregulation of SMG1 causes the reduction in the level of Upf1 phosphorylation and delays adipogenesis, suggesting the functional involvement of SMG1 in adipogenesis via SMD.

Original language	English
Pages (from-to)	1276-1287
Number of pages	12
Journal	Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume	1829
Issue number	12
DOIs	https://doi.org/10.1016/j.bbagrm.2013.10.004
Publication status	Published - 2013 Dec

Bibliographical note

Funding Information:
We thank Lynne E. Maquat for providing the NMD reporter plasmids, Luc DesGroseillers for the plasmid expressing Stau1 55 -HA 3 , Robert T. Abraham for the plasmid expressing HA-SMG1-WT or KI, Jens Lykke-Andersen for tethering plasmids, and Juan Ortín for the α-human Stau1 antibody. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A2A1A01002469). Sisu Han and Ok Hyun Park were supported in part by NRF Grant funded by the Korean Government (NRF-2011-Global PhD fellowship program and NRF-2013-Global PhD fellowship program, respectively).

Keywords

Adipogenesis
Nonsense-mediated mRNA decay
SMG1
Stau1-mediated mRNA decay
Staufen1
Upf1

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics

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10.1016/j.bbagrm.2013.10.004

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@article{99d32e64a49345ba94c494fd91e9d318,

title = "SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay",

abstract = "Suppressor of morphogenesis in genitalia 1 (SMG1), a member of the phosphatidylinositol 3-kinase-related kinase family, is involved in nonsense-mediated mRNA decay (NMD). SMG1 phosphorylates Upf1, a key NMD factor. Subsequently, hyperphosphorylated Upf1 associates with SMG5-7 or proline-rich nuclear receptor coregulatory protein (PNRC2) to elicit rapid mRNA degradation. Upf1 is also known to be involved in staufen 1 (Stau1)-mediated mRNA decay (SMD), which is closely related to NMD. However, the biological and molecular roles of SMG1 in SMD remain unknown. Here, we provide evidence that SMG1 is involved in SMD. The immunoprecipitation results show that SMG1 is complexed with Stau1, Upf1, and Dcp1a. Downregulation of SMG1 or overexpression of a kinase-inactive mutant of SMG1 inhibits SMD efficiency. In addition, downregulation of SMG1 inhibits rapid degradation elicited by artificially tethered Stau1 or Upf1 downstream of the normal termination codon. Furthermore, Stau1 and Upf1 colocalize in processing bodies in an SMG1-dependent manner. We also find that the level of SMG1 increases during adipogenesis. Accordingly, downregulation of SMG1 causes the reduction in the level of Upf1 phosphorylation and delays adipogenesis, suggesting the functional involvement of SMG1 in adipogenesis via SMD.",

keywords = "Adipogenesis, Nonsense-mediated mRNA decay, SMG1, Stau1-mediated mRNA decay, Staufen1, Upf1",

author = "Hana Cho and Sisu Han and Park, {Ok Hyun} and Kim, {Yoon Ki}",

note = "Funding Information: We thank Lynne E. Maquat for providing the NMD reporter plasmids, Luc DesGroseillers for the plasmid expressing Stau1 55 -HA 3 , Robert T. Abraham for the plasmid expressing HA-SMG1-WT or KI, Jens Lykke-Andersen for tethering plasmids, and Juan Ort{\'i}n for the α-human Stau1 antibody. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A2A1A01002469). Sisu Han and Ok Hyun Park were supported in part by NRF Grant funded by the Korean Government (NRF-2011-Global PhD fellowship program and NRF-2013-Global PhD fellowship program, respectively). ",

year = "2013",

month = dec,

doi = "10.1016/j.bbagrm.2013.10.004",

language = "English",

volume = "1829",

pages = "1276--1287",

journal = "Biochimica et Biophysica Acta - Gene Regulatory Mechanisms",

issn = "1874-9399",

publisher = "Elsevier B.V.",

number = "12",

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T1 - SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay

AU - Cho, Hana

AU - Han, Sisu

AU - Park, Ok Hyun

AU - Kim, Yoon Ki

N1 - Funding Information: We thank Lynne E. Maquat for providing the NMD reporter plasmids, Luc DesGroseillers for the plasmid expressing Stau1 55 -HA 3 , Robert T. Abraham for the plasmid expressing HA-SMG1-WT or KI, Jens Lykke-Andersen for tethering plasmids, and Juan Ortín for the α-human Stau1 antibody. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A2A1A01002469). Sisu Han and Ok Hyun Park were supported in part by NRF Grant funded by the Korean Government (NRF-2011-Global PhD fellowship program and NRF-2013-Global PhD fellowship program, respectively).

PY - 2013/12

Y1 - 2013/12

N2 - Suppressor of morphogenesis in genitalia 1 (SMG1), a member of the phosphatidylinositol 3-kinase-related kinase family, is involved in nonsense-mediated mRNA decay (NMD). SMG1 phosphorylates Upf1, a key NMD factor. Subsequently, hyperphosphorylated Upf1 associates with SMG5-7 or proline-rich nuclear receptor coregulatory protein (PNRC2) to elicit rapid mRNA degradation. Upf1 is also known to be involved in staufen 1 (Stau1)-mediated mRNA decay (SMD), which is closely related to NMD. However, the biological and molecular roles of SMG1 in SMD remain unknown. Here, we provide evidence that SMG1 is involved in SMD. The immunoprecipitation results show that SMG1 is complexed with Stau1, Upf1, and Dcp1a. Downregulation of SMG1 or overexpression of a kinase-inactive mutant of SMG1 inhibits SMD efficiency. In addition, downregulation of SMG1 inhibits rapid degradation elicited by artificially tethered Stau1 or Upf1 downstream of the normal termination codon. Furthermore, Stau1 and Upf1 colocalize in processing bodies in an SMG1-dependent manner. We also find that the level of SMG1 increases during adipogenesis. Accordingly, downregulation of SMG1 causes the reduction in the level of Upf1 phosphorylation and delays adipogenesis, suggesting the functional involvement of SMG1 in adipogenesis via SMD.

AB - Suppressor of morphogenesis in genitalia 1 (SMG1), a member of the phosphatidylinositol 3-kinase-related kinase family, is involved in nonsense-mediated mRNA decay (NMD). SMG1 phosphorylates Upf1, a key NMD factor. Subsequently, hyperphosphorylated Upf1 associates with SMG5-7 or proline-rich nuclear receptor coregulatory protein (PNRC2) to elicit rapid mRNA degradation. Upf1 is also known to be involved in staufen 1 (Stau1)-mediated mRNA decay (SMD), which is closely related to NMD. However, the biological and molecular roles of SMG1 in SMD remain unknown. Here, we provide evidence that SMG1 is involved in SMD. The immunoprecipitation results show that SMG1 is complexed with Stau1, Upf1, and Dcp1a. Downregulation of SMG1 or overexpression of a kinase-inactive mutant of SMG1 inhibits SMD efficiency. In addition, downregulation of SMG1 inhibits rapid degradation elicited by artificially tethered Stau1 or Upf1 downstream of the normal termination codon. Furthermore, Stau1 and Upf1 colocalize in processing bodies in an SMG1-dependent manner. We also find that the level of SMG1 increases during adipogenesis. Accordingly, downregulation of SMG1 causes the reduction in the level of Upf1 phosphorylation and delays adipogenesis, suggesting the functional involvement of SMG1 in adipogenesis via SMD.

KW - Adipogenesis

KW - Nonsense-mediated mRNA decay

KW - SMG1

KW - Stau1-mediated mRNA decay

KW - Staufen1

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DO - 10.1016/j.bbagrm.2013.10.004

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SN - 1874-9399

VL - 1829

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EP - 1287

JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

IS - 12

ER -

SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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