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Developmental Regulation of a proinsulin mRNA generated by intron retention

AuthorsMansilla, Alicia ; López-Sánchez, Carmen; De la Rosa, Enrique J. ; García-Martínez, Virginio; Martínez-Salas, Encarna; Pablo, Flora de ; Hernández-Sánchez, Catalina
Issue DateDec-2005
PublisherNature Publishing Group
CitationEMBO reports 6:1182-1187(2005)
AbstractProinsulin gene expression regulation and function during early embryonic development differ remarkably from those found in postnatal organisms. The embryonic proinsulin protein content decreased from gastrulation to neurulation in contrast with the overall proinsulin messenger RNA increase. This is due to increasing levels of a proinsulin mRNA variant generated by intron 1 retention in the 5′ untranslated region. Inclusion of intron 1 inhibited proinsulin translation almost completely without affecting nuclear export or cytoplasmic decay. The novel proinsulin mRNA isoform expression was developmentally regulated and tissue specific. The proportion of intron retention increased from gastrulation to organogenesis, was highest in the heart tube and presomitic region, and could not be detected in the pancreas. Notably, proinsulin addition induced cardiac marker gene expression in the early embryonic stages when the translationally active transcript was expressed. We propose that regulated unproductive splicing and translation is a mechanism that regulates proinsulin expression in accordance with specific requirements in developing vertebrates
Description6 páginas, 6 figuras -- PAGS nros. 1182-1187
Publisher version (URL)http://dx.doi.org/10.1038/sj.embor.7400539
ISSNISSN: 1469-221X
Appears in Collections:(CIB) Artículos
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