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Updated: May 6, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay
Hana Cho1, Sisu Han, Ok Hyun Park
1Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
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.
Insights
Suppressor of morphogenesis in genitalia 1 (SMG1) kinase is crucial for staufen 1-mediated mRNA decay (SMD). SMG1 regulates Upf1 phosphorylation and adipogenesis, revealing its role in SMD.
Area of Science:
- Molecular Biology
- RNA Metabolism
- Cellular Signaling
Background:
- Suppressor of morphogenesis in genitalia 1 (SMG1) is a kinase involved in nonsense-mediated mRNA decay (NMD).
- Upf1 phosphorylation by SMG1 is a key step in NMD.
- The role of SMG1 in staufen 1-mediated mRNA decay (SMD) is unknown.
Purpose of the Study:
- To investigate the biological and molecular roles of SMG1 in SMD.
- To determine if SMG1 interacts with components of the SMD pathway.
- To elucidate the function of SMG1 in adipogenesis.
Main Methods:
- Immunoprecipitation assays to detect protein complexes.
- SMG1 knockdown and kinase-inactive mutant expression to assess SMD efficiency.
- Analysis of Staufen 1 (Stau1) and Upf1 localization in processing bodies.
- Monitoring SMG1 levels and Upf1 phosphorylation during adipogenesis.
Main Results:
- SMG1 forms a complex with Stau1, Upf1, and Dcp1a.
- SMG1 downregulation or kinase-inactive mutant expression impairs SMD.
- SMG1 is required for Stau1 and Upf1 colocalization in processing bodies.
- SMG1 levels increase during adipogenesis, and its downregulation delays this process.
Conclusions:
- SMG1 plays a critical role in SMD by regulating Upf1 phosphorylation and Stau1/Upf1 localization.
- SMG1 is functionally involved in adipogenesis, potentially through SMD.
- These findings expand the known functions of SMG1 beyond NMD.
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