title: Integrator complex plays an essential role in adipose differentiation.
abstract: 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.
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Otani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Okubo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: Haruya
authors.initials: H
authors.lastname: Ohno
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kamata
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
mesh_terms: D041721:3T3-L1 Cells; D000256:Adenoviridae / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D015153:Blotting, Western; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; C110734:Ints6 protein, mouse; D046912:Multiprotein Complexes; D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C495693:Slc2a4 protein, mouse; D025521:Tumor Suppressor Proteins; D053487:DEAD-box RNA Helicases