Abstract
It is commonly known that the insulin-like growth factor-I gene contains six exons that can be differentially spliced to create multiple transcript variants. Further, there are two mutually exclusive leader exons each having multiple promoter sites that are variably used. The mature IGF-I protein derived from the multiplicity of transcripts does not differ suggesting a regulatory role for the various transcript isoforms. The variant forms possess different stabilities, binding partners, and activity indicating a pivotal role for the isoforms. Research has demonstrated differential expression of the IGF-I mRNA transcripts in response to steroids, growth hormone, and developmental cues. Many studies of different tissues have focused on assessing the presence, or putative action, of the transcript isoforms with little consideration of the transcriptional mechanisms that generate the variants or the translational use of the transcript isoforms. Control points for the latter include epigenetic regulation of splicing and promoter usage in response to development or injury, RNA binding proteins and microRNA effects on transcript stability, and preferential use of two leader exons by GH and other hormones. This review will detail the current knowledge of the mechanical, hormonal, and developmental stimuli regulating IGF-1 promoter usage and splicing machinery used to create the variants.
Highlights
It is commonly known that the insulin-like growth factor-I gene contains six exons that can be differentially spliced to create multiple transcript variants
For more than 60 years it has been known that the growth hormone – IGF-I axis is critical for body growth and maintenance
IGF-I is key to normal postnatal development: the absence of IGFI is characterized by poor prenatal growth in both the rat and human (Fu et al, 2009)
Summary
It is commonly known that the insulin-like growth factor-I gene contains six exons that can be differentially spliced to create multiple transcript variants. Inclusion or exclusion of exon 5 into the pre-pro IGF-I polypeptide gives rise to transcripts differing in E-peptide forms, termination codons, polyadenylation sites, and 3 UTR’s (Shimatsu and Rotwein, 1987; Shavlakadze et al, 2005).
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