Regulation of cytoplasmic polyadenylation can generate a bistable switch.

BMC Systems Biology
Naveed Aslam, Harel Z Shouval

Abstract

Translation efficiency of certain mRNAs can be regulated through a cytoplasmic polyadenylation process at the pre-initiation phase. A translational regulator controls the polyadenylation process and this regulation depends on its posttranslational modifications e.g., phosphorylation. The cytoplasmic polyadenylation binding protein (CPEB1) is one such translational regulator, which regulates the translation of some mRNAs by binding to the cytoplasmic polyadenylation element (CPE). The cytoplasmic polyadenylation process can be turned on or off by the phosphorylation or dephosphorylation state of CPEB1. A specific example could be the regulation of Calcium/Calmodulin-dependent protein kinase II (αCaMKII) translation through the phosphorylation/dephosphorylation cycle of CPEB1. Here, we show that CPEB1 mediated polyadenylation of αCaMKII mRNA can result in a bistable switching mechanism. The switch for regulating the polyadenylation is based on a two state model of αCaMKII and its interaction with CPEB1. Based on elementary biochemical kinetics a high dimensional system of non-linear ordinary differential equations can describe the dynamic characteristics of the polyadenylation loop. Here, we simplified this high-dimensional syste...Continue Reading

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Citations

Jan 26, 2016·Nature Reviews. Neuroscience·Paul SmolenJohn H Byrne
Jun 19, 2013·Wiley Interdisciplinary Reviews. RNA·Amanda CharlesworthCornelia H de Moor
Sep 14, 2013·Current Biology : CB·Mara C Inniss, Pamela A Silver

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