The heterogenous nuclear riboprotein S1-1 regulates AT1 receptor gene expression via transcriptional and posttranscriptional mechanisms.
The AT1 receptor plays an essential role in the pathogenesis of atherosclerosis. AT1 receptor expression is predominately mediated via mRNA destabilization by mRNA binding proteins. We identified via MALDI-analysis the heterogenous nuclear riboprotein S1-1 as an important regulator of AT1 receptor mRNA stability. The S1-1 protein possesses multiple nucleolar and cellular functions in vascular smooth muscle cells (VSMC). Overexpression of S1-1 sense resulted in VSMC in significant stabilization of AT1 receptor mRNA. However, this stabilization of the AT1 receptor mRNA is accompanied by a significantly reduced AT1 receptor mRNA transcription as shown via nuclear run-on assay resulting finally in reduced AT1 receptor mRNA levels. Additionally, S1-1 overexpression leads to increased apoptosis in VSMC and decreases VSMC proliferation.
Mueller
Cornelius F H
CF
Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Bonn, Germany. cornelius.mueller@ukb.uni-bonn.de
Berger
Anja
A
Zimmer
Sebastian
S
Tiyerili
Vedat
V
Nickenig
Georg
G
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C101166:Rbm10 protein, rat; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II