Prokaryotic Translation Regulation

In most organisms, the overall control of protein biosynthesis occurs primarily at the transcriptional level. In some cases, however, regulation occurs at the translational level.

The major translational control step is initiation. There are at least three mechanisms of initiation control:

> 1. mRNA tertiary structure may prevent attachment to the 30S ribosomal unit - Figure 27.31 illustrates this mechanism for the RNA of the MS2 bacteriophage. Here the coding for the A protein at the 5' end of the polycistronic message is needed in small quantities, whereas the other proteins are needed in larger quantities. Most of the time, the 5' end of the A gene where translation would start is blocked by tertiary folding of the mRNA and only rarely available. Translation occurs preferentially at more accessible sites internal to the A gene.

> 2. Proteins may bind to the mRNA, blocking initiation - Ribosomal proteins bind to their own mRNAs. This seems to occur because the mRNA tertiary structure resembles the normal binding site for that protein on rRNA. Figure 27.32 illustrates the process. The regulation works well, because when there is abundant rRNA in the cell, the proteins preferentially bind to it instead of their own messages. When there are only low levels of rRNA, however, the proteins bind their own messsages and prevent further proteins from being made. rRNA required for translation is under metabolic control. Starvation for amino acids in prokaryotes results in the accumulation of the unusual nucleotides ppGpp and pppGpp, which inhibit the synthesis of rRNA. This, in turn, inhibits ribosomal protein synthesis by the above mechanism.

> 3. Antisense RNA may block initiation. An antisense sequence blocks the initiation site by forming a double-stranded structure, as shown for the translation of transposase mRNA in Figure 27.33. The selective blocking of the translation of specific messages by antisense RNA also has applications in the treatment of disease and cancer. One major difficulty in employing antisense RNAs in the treatment of disease, however, is in getting the molecules into the target cells. RNA molecules are negatively charged so they do not traverse membranes easily. Moreover, once inside the cells, they are subject to enzymatic degradation.

See also: Structure of Prokaryotic mRNAs, Initiation of Translation, Elongation of Translation, Termination of Translation

INTERNET LINK: Control of Translation Initiation in Prokaryotes