title: The heterogenous nuclear riboprotein S1-1 regulates AT1 receptor gene expression via transcriptional and posttranscriptional mechanisms.
abstract: 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.
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Bonn, Germany. cornelius.mueller@ukb.uni-bonn.de
authors.forename: Cornelius F H
authors.initials: CF
authors.lastname: Mueller
authors.forename: Anja
authors.initials: A
authors.lastname: Berger
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zimmer
authors.forename: Vedat
authors.initials: V
authors.lastname: Tiyerili
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
mesh_terms: 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
chemical_list: 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