کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3001430 1180637 2014 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PTBP1 is required for glucose-stimulated cap-independent translation of insulin granule proteins and Coxsackieviruses in beta cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی سیستم های درون ریز و اتونومیک
پیش نمایش صفحه اول مقاله
PTBP1 is required for glucose-stimulated cap-independent translation of insulin granule proteins and Coxsackieviruses in beta cells
چکیده انگلیسی

Glucose and GLP-1 stimulate not only insulin secretion, but also the post-transcriptional induction of insulin granule biogenesis. This process involves the nucleocytoplasmic translocation of the RNA binding protein PTBP1. Binding of PTBP1 to the 3′-UTRs of mRNAs for insulin and other cargoes of beta cell granules increases their stability. Here we show that glucose enhances also the binding of PTBP1 to the 5′-UTRs of these transcripts, which display IRES activity, and their translation exclusively in a cap-independent fashion. Accordingly, glucose-induced biosynthesis of granule cargoes was unaffected by pharmacological, genetic or Coxsackievirus-mediated inhibition of cap-dependent translation. Infection with Coxsackieviruses, which also depend on PTBP1 for their own cap-independent translation, reduced instead granule stores and insulin release. These findings provide insight into the mechanism for glucose-induction of insulin granule production and on how Coxsackieviruses, which have been implicated in the pathogenesis of type 1 diabetes, can foster beta cell failure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Metabolism - Volume 3, Issue 5, August 2014, Pages 518–530
نویسندگان
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