کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1947117 1054296 2007 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Translational regulation of PGHS-1 mRNA: 5′ untranslated region and first two exons conferring negative regulation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Translational regulation of PGHS-1 mRNA: 5′ untranslated region and first two exons conferring negative regulation
چکیده انگلیسی

Prostaglandin endoperoxide H synthase-1 gene expression is described as inducible in a few contexts such as differentiation of megakaryoblastic MEG-01 cells into platelet-like structures. In the MEG-01 cells model of PGHS-1 gene induction, we previously reported a delay in protein synthesis and identified the translational step of gene expression as being regulated. In the current study, we mapped PGHS-1 mRNA sequences regulating translational efficiency and identified an RNA binding protein. The 5′UTR and first two exons of the PGHS-1 5′ mRNA decreased the synthesis of Luciferase protein by approximately 80% without significant changes in mRNA levels when compared to controls. Both the PGHS-1 5′-UTR and the first two exons were required for activity. Sucrose density gradient fractionations of cytoplasmic extracts from MEG-01 cells infected with reporter constructs, either controls or containing PGHS-1 sequence, presented a similar profile of distribution of reporter transcripts between polysomal and non-polysomal fractions. RNA/protein interaction studies revealed nucleolin binding to the 135 nt PGHS-1 sequence. Mutation of the two NRE elements located in the 5′end of PGHS-1 mRNA sequence partially reduced the negative activity of the 135 nt sequence. Stable secondary structures predicted at the 5′ end of the transcript are potentially involved in translational regulation. We propose that the 5′end of PGHS-1 mRNA represses translation and could delay the synthesis of PGHS-1 enzyme.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression - Volume 1769, Issue 2, February 2007, Pages 92–105
نویسندگان
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