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- FGF-2, fibroblast growth factor 2
- FMRP, fragile X mental retardation protein
- GM-CSF, granulocyte macrophage colony stimulating factor
- IGF, insulin like growth factor
- IL, interleukin
- IRE, iron responsive element
- IRP, iron responsive protein
- TGFβ, transforming growth factor β
- TNFα, tumour necrosis factor α
- UTR, untranslated region
- VEGF, vascular endothelial growth factor
An important mechanism for regulating protein expression
In 2001, the first draft of the human genome was published.1,2 Paediatricians from all disciplines can look forward to important and novel insights into the genetic basis for numerous diseases that affect children and their families. The surprising finding that our genome consists of 30–40 000 genes, only slightly larger than that of the plant Arabidopsis thalania (25 498 genes),3 has now focused scientific study towards protein expression (termed proteomics), which is considerably more complex. It is also becoming apparent that defects in the mechanisms of protein expression are associated with human disease.
Since Watson and Crick described the structure of DNA in 1953, molecular biologists have done much to clarify the processes by which the genes contained in DNA are converted into proteins. Production of protein depends on transcription of the gene, which is controlled by a large number of factors interacting with various regulatory elements associated with the gene.4 Pre-mRNA undergoes alternate splicing and other processing, before cytosolic translation of the messenger RNA (mRNA) results in protein. A number of diseases are known to be associated with abnormalities of transcriptional control (reviewed by Semenza5). However, increasingly we are realising that translational regulation is important both in physiological and pathological processes.
TRANSLATIONAL REGULATION
Regulation can be global—that is, affecting the translation of all cellular mRNA, or specific to an individual mRNA. In the latter case the protein coding region is flanked by non-coding sequences—the untranslated regions (UTRs). Various regulatory molecules bind to specific sequences within the UTR, which may be on either side of the coding region, to either inhibit or enhance translation (fig 1). To add further complexity, different molecules can interact with the regulatory molecules to enhance or inhibit their effects. Control of protein expression from existing …