Читать книгу Essential Endocrinology and Diabetes - Richard I. G. Holt - Страница 38

mRNA is transported to the ribosomes, where protein synthesis occurs by ‘translation’ (Figure 2.3a). The ribosomes are attached to the outside of the endoplasmic reticulum (ER), leading to the description of ‘rough ER’. The ribosome is an RNA–protein complex that reads the mRNA sequence in groups of three nucleotides, called a codon. Each codon represents an amino acid. The start codon is the sequence of A–U–G nucleotides (corresponding to ATG in the genomic DNA) and specifies the amino acid methionine (Figure 2.2). From this point onwards, translation continues until a ‘stop’ codon is encountered (UAA, UGA or UAG).

By understanding these normal events of gene transcription and protein translation, it becomes possible to appreciate how mutations (sequence errors) in the genomic DNA lead to a miscoded, and consequently malfunctional, protein (Box 2.2). An entire gene may be missing (‘deleted’) or duplicated. An erroneous base pair in an enhancer or the promoter region may impair binding of a critical transcription factor and lessen a gene’s expression. A similar error in a coding exon might translate a different amino acid or even miscode a premature stop codon. Small deletions or insertions of one or two base pairs throw the whole triplet code out of frame. A mutation at the boundary between an intron and an exon can corrupt splicing so that the intron is included in the mature mRNA. All of these genetic events can affect endocrinology either as developmental disorders when that the fault is likely to be present in all or many of the body’s cells, or as acquired change later in life, potentially predisposing to the formation of an endocrine tumour (Chapter 10).

Figure 2.3 (a) Peptide hormone‐synthesizing and (b) steroid hormone‐synthesizing cells. In (b), cholesterol enters the cell via the low‐density lipoprotein receptor which is internalized.