Translation Control by Proteins


Translation control by proteins refers to the process by which protein synthesis of specific products is regulated by external trans‐acting proteins, often by repression and sometimes autoregulatory on the messenger ribonucleic acid (mRNA) encoding the very protein being synthesized, and also by activation in some systems.

Keywords: RNA phage gene regulation; phage T4 gene regulation; ribosomal protein synthesis; translation activation; iron homeostasis; SELEX

Figure 1.

Collision course averted in RNA phage growth. (a) Synthesis of phage minus‐strand RNA requires the template to be copied in the opposite direction from which ribosomes move on the same RNA during translation. To avoid collision, translational repression makes the RNA translationally dormant, so that replication can proceed unimpeded. (b) Synthesis of phage RNA plus strands by replicase proceeds in the same direction as ribosome movement.

Figure 2.

T4 gene 32 autoregulation. A pseudoknot in the mRNA at the 5′ end is the nucleation point for binding to the mRNA of gene 32 protein monomers, depicted as filled half‐circles. The horizontal hatchmarks in the pseudoknot represent hydrogen bonds in the two stems of this structure. Binding of gene 32 protein is cooperative and proceeds downstream until the ribosome‐binding site (rbs) and the start codon (AUG) are coated with gene 32 protein, thereby blocking access of ribosomes to the translation start of the gene 32 coding region.

Figure 3.

The principle of SELEX (systematic evolution of ligands by exponential enrichment). A random pool of RNAs (typically with a diversity of 1014), generated by mixed nucleotide incorporation during oligonucleotide synthesis, is designed with fixed sequences attached at both ends (shown as small rectangles). This RNA pool is bound to a protein target, immobilized (e.g. on a nitrocellulose filter), and unbound RNAs are washed away. Bound RNAs are eluted and amplified by reverse transcriptase polymerase chain reaction (RT‐PCR), using the fixed sequences at the ends to bind appropriate primers. The products of this reaction are transcribed (e.g. by T7 RNA polymerase), creating an enriched pool for another round of binding to target. This cycle is repeated in multiple rounds (as many as 12 or more), to yield a collection of RNAs with high affinity for the target protein.

Figure 4.

(a) Regulation of the E. coli r‐protein ‘streptomycin’ operon. Ribosomal protein S7 acts as a translational repressor of this operon, binding to target sites near the translation starts for itself and for EF‐G synthesis, blocking ribosome access. Because synthesis of EF‐G is translationally coupled to synthesis of EF‐Tu, blocking EF‐G synthesis also blocks EF‐Tu synthesis. Binding of the S7 repressor also destabilizes the mRNA upstream of the binding site (encoding S12), thus preventing S12 synthesis as well. P, promoter; rbs, ribosome‐binding site; AUG, translation start codon. (b) and (c), example of molecular mimicry. Model of secondary structure of E. coli r‐protein L1 binding sites on 23S rRNA (b) and on mRNA from the operon containing the genes encoding L11 and L1 (c). Nucleotide sequences in red indicate homology; numbering denotes nucleotide positions in their respective primary sequences. Parts (b) and (c) are based on Thomas and Nomura (1987) Nucleic Acids Research15: 3085–3096.

Figure 5.

Regulation of transferrin receptor mRNA stability by iron‐responsive element–iron‐regulatory protein (IRE–IRP) interactions in the 3′ untranslated region. Five IREs (A–E) and other structural features are depicted. The regulatory region consists of two areas that are separated by the large loop on the right and that may be brought into closer proximity by long range RNA–RNA interactions. IRP binding in the absence of iron (a) protects the mRNA from an initial endonucleolytic clip, which occurs (presumably in a region between IREC and IRED) when the transcript is not protected in the presence of iron (b). ORF, open reading frame. Reproduced with permission from Hentze and Kuhn (1996) Proceedings of the National Academy of Sciences of the USA93: 8175–8182. Copyright © 1996 National Academy of Sciences, USA.


Further Reading

Fox TD (1996) Translational control of endogenous and recoded nuclear genes in yeast mitochondria: regulation and membrane targeting. Experientia 52: 1130–1135.

Gebauer F and Hentze MW (2004) Molecular mechanisms of translational control. Nature Reviews Molecular Cell Biology 5: 827–835.

Gold L (1988) Posttranscriptional regulatory mechanisms in E. coli. Annual Review of Biochemistry 57: 199–233.

Gold L, Brown D, He Y et al. (1997) From oligonucleotide shapes to genomic SELEX: novel biological regulatory loops. Proceedings of the National Academy of Sciences of the USA 94: 59–64.

Hattman S (1999) Unusual transcriptional and translational regulation of the bacteriophage Mu mom operon. Pharmacology and Therapeutics 84: 367–388.

Hershey JW (1991) Translational control in mammalian cells. Annual Review of Biochemistry 60: 717–755.

Klausner RD, Rouault TA and Harford JB (1993) Regulating the fate of mRNA: the control of cellular iron metabolism. Cell 72: 19–18.

Mathews MB, Sonenberg N and Hershey JWB (eds) (2007) Translational Control in Biology and Medicine. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Nomura M (1999) Regulation of ribosome biosynthesis in E. coli and Saccharomyces cerevisiae: diversity and common principles. Journal of Bacteriology 181: 6857–6864.

Nomura M, Gourse R and Baughman G (1984) Regulation of the synthesis of ribosomes and ribosomal components. Annual Review of Biochemistry 53: 75–117.

Sonenberg N, Hershey JWB and Mathews MB (eds) (2000) Translational Control of Gene Expression. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Witherell GW, Gott JM and Uhlenbeck OC (1991) Specific interaction between RNA phage coat proteins and RNA. Progress in Nucleic Acid Research and Molecular Biology 40: 185–220.

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How to Cite close
Goldman, Emanuel(Dec 2007) Translation Control by Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000860.pub2]