[HTML][HTML] PTBP1 is required for glucose-stimulated cap-independent translation of insulin granule proteins and Coxsackieviruses in beta cells
KP Knoch, S Nath-Sain, A Petzold, H Schneider… - Molecular …, 2014 - Elsevier
KP Knoch, S Nath-Sain, A Petzold, H Schneider, M Beck, C Wegbrod, A Sönmez, C Münster…
Molecular Metabolism, 2014•ElsevierGlucose 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 …
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 …
Abstract
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.
Elsevier