Mosaic evolution of the insulin-like growth factors. Organization, sequence, and expression of the rat insulin-like growth factor I gene.

A Shimatsu,P Rotwein

doi:10.1016/s0021-9258(18)47652-1

Abstract

Insulin-like growth factor I (IGF-I) plays a major role in mammalian growth and regenerative processes as a mediator of many of the biological effects of growth hormone. We have demonstrated recently that the human IGF-I gene is transcribed and processed into distinct messenger RNA molecules, each of which directs the synthesis of unique IGF-I-containing peptides. As a means to determine whether a similar model of IGF-I gene organization and expression is the paradigm in mammals and as an initial step in devising experimental approaches to the study of regulation of IGF-I biogenesis, we have isolated and characterized the rat IGF-I gene. The rat gene, like its human counterpart, is very large, extending over at least 73 kilobases, and is composed of five exons subdivided by four introns. As in the human example, the rat IGF-I gene hybridizes to several messenger RNAs: 0.8-1.2, 1.6-2.1, and 7.8 kilobases. There is extensive nucleotide and amino acid sequence conservation between the two genes. The predicted mature rat IGF-I protein is identical to the human peptide in 67 of 70 residues. A comparably high degree of amino acid sequence identity is also found for both the amino- and carboxyl-terminal extension peptides, suggesting that, like mature IGF-I, the extension molecules may have physiological function.

Highlights

We have demonstrated recently that the human insulin-like growth factors (IGFs)-Igene is transcribed and processedinto distinct messenger RNA molecules, each of which directs the synthesis of unique Insulin-like growth factor I (IGF-I)-containing peptides
The insulin-like growth factors (IGFs),’ or somatomedins, comprise a family of peptides which circulate in blood and play major roles in mammalian development and growth [1, 2]
Genomic Southern Blot Analysis: Rat IGF-Z GeneIs Single Copy-In order to determine the feasibility of using human IGF-I cDNA or genomic clones as probes to isolate the corresponding rat sequences and in order to define the copy number of the raItGF-I gene,we performed genomiSc outhern blots using radiolabeled human IGF-IA and IGF-IB cDNAs as hybridization probes.As seen in Fig. 1,both IGF-I cDNAs identify a discrete set of bands in rat chromosomal DNA

Summary

Introduction

As in the human example, the rat IGF-I gene hybridizes to several messenger RNAs: 0.8-1.2, 1.62.1, and 7.8 kilobases. The predicted mature rat IGF-I protein is identical to the human peptide in 67 of 7 0 residues. In addition to similaritiesin structure, there is extensive nucleotide and amino acid conservation between the two genes and comparable expression as multiple messenger RNA species.

Results

Conclusion