Integrator complex plays an essential role in adipose differentiation

Autor: Otani, Y., Nakatsu, Y., Sakoda, H., Fukushima, Toshiaki, Fujishiro, M., Kushiyama, A., Okubo, H., Tsuchiya, Y., Ohno, H., Takahashi, S., Nishimura, F., Kamata, H., Katagiri, H., Asano, T.
Rok vydání: 2013
Předmět:
Small interfering RNA
Time Factors
RNA
Messenger/genetics/metabolism
Integrator complex
Cellular differentiation
PPAR gamma/genetics/metabolism
Blotting
Western
RNA
Small Interfering/genetics/metabolism
Biophysics
Glucose Transporter Type 4/genetics/metabolism
Adipose tissue
Biology
Fatty Acid-Binding Proteins
Transfection
Biochemistry
DEAD-box RNA Helicases/genetics/*metabolism
Adenoviridae
DEAD-box RNA Helicases
Mice
3T3-L1 Cells
Adipocytes
Animals
RNA
Messenger
RNA
Small Interfering
Adenoviridae/metabolism
Adipogenesis
Molecular Biology
Transcription factor
Regulation of gene expression
Glucose Transporter Type 4
Adipocytes/*cytology/metabolism
Tumor Suppressor Proteins
RNA-Binding Proteins
Fibroblasts/cytology/metabolism
Cell Biology
Fibroblasts
Molecular biology
Fatty Acid-Binding Proteins/genetics/metabolism
PPAR gamma
Multiprotein Complexes/genetics/*metabolism
Gene Expression Regulation
Multiprotein Complexes
Perilipin
Zdroj: Biochemical and Biophysical Research Communications. 434:197-202
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2013.03.029
Popis: The dynamic process of adipose differentiation involves stepwise expressions of transcription factors and proteins specific to the mature fat cell phenotype. In this study, it was revealed that expression levels of IntS6 and IntS11, subunits of the Integrator complex, were increased in 3T3-L1 cells in the period when the cells reached confluence and differentiated into adipocytes, while being reduced to basal levels after the completion of differentiation. Suppression of IntS6 or IntS11 expression using siRNAs in 3T3-L1 preadipocytes markedly inhibited differentiation into mature adipocytes, based on morphological findings as well as mRNA analysis of adipocyte-specific genes such as Glut4, perilipin and Fabp4. Although Pparγ2 protein expression was suppressed in IntS6 or IntS11-siRNA treated cells, adenoviral forced expression of Pparγ2 failed to restore the capacity for differentiation into mature adipocytes. Taken together, these findings demonstrate that increased expression of Integrator complex subunits is an indispensable event in adipose differentiation. Although further study is necessary to elucidate the underlying mechanism, the processing of U1, U2 small nuclear RNAs may be involved in cell differentiation steps.
Databáze: OpenAIRE
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