Transcriptional Regulation

The first step in gene expression is the transcription of the coding DNA sequences to discrete RNA molecules. Specific DNA regions, defined as promoters, are recognized by the transcribing enzyme, a DNA-dependent RNA polymerase (RNAP). The RNAP binds to the promoter and initiates the synthesis of the RNA transcript. The enzyme catalyzes the sequential addition of ribonucleotides to the growing RNA chain in a template-dependent manner until it comes to a termination signal ('terminator'). The DNA sequence between the start point and the termination point defines a 'transcription unit'. An RNA transcript can include one gene or more. Its sequence is identical to one strand of the DNA, the coding strand, and complementary to the other, which provides the template. The base at the start point is defined as +1 and the one before that as -1. Positive numbers are increased going downstream (into the transcribed region), whereas negative numbers increase going upstream. The immediate product of transcription, which extends from the promoter to the terminator, is termed as 'primary transcript'. In prokaryotes, messenger RNA (mRNA) is usually translated concomitantly while being transcribed and is rapidly degraded when not protected by the ribosomes, whereas ribosomal RNA (rRNA) and transfer RNA (tRNA) are cleaved to give mature products and are stable. Transcription is the principal step at which gene expression is controlled. Many factors, such as DNA signals, regulatory proteins, noncoding RNAs, and small ligands (nucleotides, metabolites), determine whether the polymerase will choose to transcribe a certain gene and whether the whole process of transcription will be accomplished successfully. The timing of transcription of specific genes is influenced by environmental conditions and by the growth cycle phase. The molecular picture of how genes are transcribed and the nature of the regulatory mechanisms that control transcription are far from being complete, but lots of progress has been made. Work on relatively simple organisms, bacteriophage, and bacteria has provided new insights into the mechanisms that are involved in the regulation of gene expression, transcriptional control mechanisms being among them. Although there are significant differences in the organization of individual genes and in the details and the complexity of the regulatory mechanisms among prokaryotes and eukaryotes, it is clear that basic principles are shared among all organisms. Due to the relative simplicity of prokaryotic biochemical pathways, their easy manipulation in the laboratory, and the advanced tools that are available for changing their genotype and for testing the resulting phenotype, it is easier to infer these basic principles by studying prokaryotes.