Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides

H. Yang, Martin L Adamo, A. P. Koval, M. C. McGuinness, H. Ben-Hur, Y. Yang, D. LeRoith, C. T. Roberts

Research output: Contribution to journalArticle

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Abstract

Rat insulin-like growth factor I (IGF-I) mRNAs contain multiple 5'- untranslated regions due to the use of leader exons transcribed from several transcription initiation sites and to alternative splicing within-leader exon 1. Synthetic RNAs with 5'-ends corresponding to the use of exon 1 transcription initiation sites were translated in vitro into prepro-IGF-I peptides initiated at a Met-48 codon in exon 1 or a Met-22 codon in exon 3, and RNAs with a 5'-end corresponding to the major exon 2 transcription start site were translated into a prepro-IGF-I peptide initiated at a Met-32 codon in exon 2. All forms of prepro-IGF-I were processed by canine pancreatic microsomes, suggesting that all these prepeptides function as signal peptides. The translational efficiency of IGF-I RNAs was inversely proportional to the length of the 5'-untranslated region. Mutation of the first of three upstream AUG codons in exon 1, which potentially initiates a 14-amino acid open reading frame, did not affect prepro-IGF-I translation. The other two AUG codons are immediately followed by stop codons. The absence of both upstream AUG codons in a completely spliced exon 1-derived RNA enhanced the in vitro and in vivo translatability of this RNA as compared with the full-length RNA. Mutation of the downstream initiation codon in particular increased translational efficiency in vitro and in intact cells, suggesting that an inefficient reinitiation event at the Met-48 codon contributes to the poorer translation of IGF-I mRNAs in which these upstream AUGUGA motifs occur. We conclude that IGF-I mRNAs potentially encode multiple forms of preproIGF and that specific differences in their 5'-untranslated regions provide a molecular basis for translational control of IGF-I biosynthesis.

Original languageEnglish (US)
Pages (from-to)1380-1395
Number of pages16
JournalMolecular Endocrinology
Volume9
Issue number10
StatePublished - 1995

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Protein Sorting Signals
Insulin-Like Growth Factor I
Exons
Codon
Messenger RNA
RNA
5' Untranslated Regions
Transcription Initiation Site
Peptides
Mutation
Initiator Codon
Terminator Codon
Alternative Splicing
Microsomes
Open Reading Frames
Canidae
Amino Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Yang, H., Adamo, M. L., Koval, A. P., McGuinness, M. C., Ben-Hur, H., Yang, Y., ... Roberts, C. T. (1995). Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides. Molecular Endocrinology, 9(10), 1380-1395.

Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides. / Yang, H.; Adamo, Martin L; Koval, A. P.; McGuinness, M. C.; Ben-Hur, H.; Yang, Y.; LeRoith, D.; Roberts, C. T.

In: Molecular Endocrinology, Vol. 9, No. 10, 1995, p. 1380-1395.

Research output: Contribution to journalArticle

Yang, H, Adamo, ML, Koval, AP, McGuinness, MC, Ben-Hur, H, Yang, Y, LeRoith, D & Roberts, CT 1995, 'Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides', Molecular Endocrinology, vol. 9, no. 10, pp. 1380-1395.
Yang, H. ; Adamo, Martin L ; Koval, A. P. ; McGuinness, M. C. ; Ben-Hur, H. ; Yang, Y. ; LeRoith, D. ; Roberts, C. T. / Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides. In: Molecular Endocrinology. 1995 ; Vol. 9, No. 10. pp. 1380-1395.
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