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Upstream AUGs in embryonic proinsulin mRNA control its low translation level

Proinsulin is expressed prior to development of the pancreas and promotes cell survival. Here we study the mechanism affecting the translation efficiency of a specific embryonic proinsulin mRNA. This transcript shares the coding region with the pancreatic form, but presents a 32 nt extended leader r...

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Hauptverfasser: Hernández‐Sánchez, Catalina (VerfasserIn) , Mansilla, Alicia (VerfasserIn) , Pollerberg, G. Elizabeth (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 October 2003
In: The EMBO journal
Year: 2003, Jahrgang: 22, Heft: 20, Pages: 5582-5592
ISSN:1460-2075
DOI:10.1093/emboj/cdg515
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1093/emboj/cdg515
Verlag, kostenfrei, Volltext: http://emboj.embopress.org/content/22/20/5582
Volltext
Verfasserangaben:Catalina Hernández‐Sánchez, Alicia Mansilla, Enrique J. de la Rosa, G. Elisabeth Pollerberg, Encarna Martínez‐Salas and Flora de Pablo
Beschreibung
Zusammenfassung:Proinsulin is expressed prior to development of the pancreas and promotes cell survival. Here we study the mechanism affecting the translation efficiency of a specific embryonic proinsulin mRNA. This transcript shares the coding region with the pancreatic form, but presents a 32 nt extended leader region. Translation of proinsulin is markedly reduced by the presence of two upstream AUGs within the 5′ extension of the embryonic mRNA. This attenuation is lost when the two upstream AUGs are mutated to AAG, leading to translational efficiency similar to that of the pancreatic mRNA. The upstream AUGs are recognized as initiator codons, because expression of upstream ORF is detectable from the embryonic transcript, but not from the mutated or the pancreatic mRNAs. Strict regulation of proinsulin biosynthesis appears to be necessary, since exogenous proinsulin added to embryos in ovo decreased apoptosis and generated abnormal developmental traits. A novel mechanism for low level proinsulin expression thus relies on upstream AUGs within a specific form of embryonic proinsulin mRNA, emphasizing its importance as a tightly regulated developmental signal.
Beschreibung:Gesehen am 08.05.2017
Beschreibung:Online Resource
ISSN:1460-2075
DOI:10.1093/emboj/cdg515

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