Developmental regulation of a proinsulin messenger RNA generated by intron retention.
Proinsulin 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.
Mansilla
Alicia
A
Group of Growth Factors in Vertebrate Development, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain.
López-Sánchez
Carmen
C
de la Rosa
Enrique J
EJ
García-Martínez
Virginio
V
Martínez-Salas
Encarna
E
de Pablo
Flora
F
Hernández-Sánchez
Catalina
C
D020121:5' Untranslated Regions; D000818:Animals; D002642:Chick Embryo; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D007438:Introns; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D009420:Nervous System / Q000196:embryology; D011384:Proinsulin / Q000032:analysis / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D014615:Vaccinia / Q000821:virology
D020121:5' Untranslated Regions; D011498:Protein Precursors; D012333:RNA, Messenger; D011384:Proinsulin