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FLORA DE PABLO Y COLS. AN. R. ACAD. NAC. FARM.

FIGURE 3. Schematic representation of different embryonic and pancreatic proinsulin
mRNA transcripts. Exons (e) and intron 1 (int) are represented. The arrow above
indicates the translation initiation site. The techniques used were 5’RACE and

RT-PCR with total RNA from pancreas and E1.5 chick embryos.

Exon 1 of the embryo had an extension of 32 nucleotides with
respect to exon 1 of the pancreas (19) yielding two mRNAs that we
termed Pro1B and Pro1A, respectively. The protein product in both
cases was proinsulin. Translation of the embryonic form is markedly
downregulated by the presence of two upstream AUGs within the 32
nucleotide extension of the Pro1B mRNA (19). A later approach using
PCR confirmed the expression from gastrulation to organogenesis
of the Pro1B transcript, and revealed another alternative proinsulin
transcript, a form that retained intron 1 (717 nucleotides) (28)
(Fig. 3). Termed Pro1B1, it is a mature cytoplasmic mRNA but its
translational capacity is nearly blocked due to its long leader region.
There was differential developmental regulation of this new mRNA,
with increasing abundance from gastrulation to neurulation and
organogenesis.

We wonder whether this highly sophisticated regulation of
proinsulin expression had any possible physiological implication and
tried to look at events in early development that may be modulated
by insulin or proinsulin.

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