Translation Control by RNA


Translation control by RNA (ribonucleic acid) refers to the process by which protein synthesis is regulated by structural elements in RNA (primary, secondary or tertiary), often cis‐acting in the messenger RNA encoding the protein being synthesized, and also trans‐acting in a number of systems.

Keywords: RNA bacteriophage; antisense RNA; mRNA stability; translational coupling; translational enhancers; translational attenuation; codon bias

Figure 1.

Translational control in RNA phage. Schematic diagram depicts the principle of how RNA structure governs relative translation of the coat and replicase protein genes. Note that protein synthesis proceeds, as always, from the 5′ to 3′ direction (indicated) on the messenger RNA (mRNA). (a) The ribosome‐binding site (rbs) and the start codon (AUG) of the coat protein are exposed and accessible to ribosomes so that translation of the coat gene proceeds readily. However, the rbs and the AUG (read right to left) of the replicase gene are buried in the RNA structure (selected hydrogen bonds are depicted as short vertical lines between the upper and lower portions of the RNA chain) and not accessible to ribosomes, so this gene is not translated unless the structure is opened up. (b) Ribosomes translating the upstream coat gene open the RNA structure when they proceed past approximately codons 30–40 (indicated earlier the upper portion of the RNA chain), allowing the replicase gene, rbs and AUG to be accessible to other ribosomes, which can now start translating the replicase gene.

Figure 2.

Example of prokaryotic RNA secondary structure control. Schematic diagram depicts the principle of how alternate forms of messenger RNA (mRNA) can lead to either inhibition or expression. A longer form of the mRNA, starting from promoter P1, folds into a structure such that the ribosome‐binding site (rbs) and the start codon (AUG) are occluded in a stem–loop, and are inaccessible to ribosomes. A shorter form of the mRNA, starting from promoter P2, does not form the inhibitory structure, therefore the rbs and AUG are available for ribosomes to commence translation.

Figure 3.

Model of translational attenuation. The ribosome‐binding site (rbs) and start codon (AUG) for the antibiotic resistance gene are masked by the secondary structure of the message in (a), therefore ribosomes cannot translate the message for the resistance gene. However, when ribosomes begin translation at the rbs and AUG of the upstream translation start in the leader region, and a short nascent leader peptide is synthesized, the ribosomes will stall during translation of the leader peptide in the presence of sublethal concentrations of antibiotic. This opens up the secondary structure, exposing the translation start site for the resistance gene, which is now expressed, as shown in (b).

Figure 4.

Schematic drawing of how antisense RNA inhibits translation of a target message. The ribosome‐binding site (rbs) and start codon (AUG) to initiate translation of a coding region is accessible to ribosomes in (a). Antisense RNA encompassing the translation initiation region binds to the mRNA, and obscures the start site from ribosomes in (b). Note that the orientation of the antisense RNA is antiparallel to mRNA, i.e. 5′ to 3′ is in the opposite direction.



Arini A, Keller MP and Arber W (1997) An antisense RNA in IS30 regulates the translational expression of the transposase. Biological Chemistry 378: 1421–1431.

Baim SB and Sherman F (1988) mRNA structures influencing translation in the yeast Saccharomyces cerevisiae. Molecular and Cellular Biology 8: 1591–1601.

Baranov PV, Gesteland RF and Atkins JF (2002) Recoding: translational bifurcations in gene expression. Gene 286: 187–201.

Barrick D, Villanueba K, Childs J et al. (1994) Quantitative analysis of ribosome binding sites in E. coli. Nucleic Acids Research 22: 1287–1295.

Bechhofer DH (1990) Triple post‐transcriptional control. Molecular Microbiology 4: 1419–1423.

Berkhout B, Schmidt BF, van Strien A et al. (1987) Lysis gene of bacteriophage MS2 is activated by translation termination at the overlapping coat gene. Journal of Molecular Biology 195: 517–524.

Bordier B, Perala‐Heape M, Degols G et al. (1995) Sequence‐specific inhibition of human immunodeficiency virus (HIV) reverse transcription by antisense oligonucleotides: comparative study in cell‐free assays and in HIV‐infected cells. Proceedings of the National Academy of Sciences of the USA 92: 9383–9387.

Brown L and Elliott T (1997) Mutations that increase expression of the rpoS gene and decrease its dependence on hfq function in Salmonella typhimurium. Journal of Bacteriology 179: 656–662.

Celesnik H, Deana A and Belasco JG (2007) Initiation of RNA decay in E. coli by 5′ pyrophosphate removal. Molecular Cell 27: 79–90.

Chandler M and Fayet O (1993) Translational frameshifting in the control of transposition in bacteria. Molecular Microbiology 7: 497–503.

Chevallier A and Garel JP (1982) Differential synthesis rates of tRNA species in the silk gland of Bombyx mori are required to promote tRNA adaptation to silk messages. European Journal Biochemistry 124: 477–482.

Chiaruttini C, Milet M and Springer M (1997) Translational coupling by modulation of feedback repression in the IF3 operon of E. coli. Proceeding of the National Academy of Sciences of the USA 94: 9208–9213.

Condon C (2007) Maturation and degradation of RNA in bacteria. Current Opinion in Microbiology 10: 271–278.

Davis MA, Simons RW and Kleckner N (1985) Tn10 protects itself at two levels from fortuitous activation by external promoters. Cell 43: 379–387.

Flynn A and Proud CG (1996) The role of eIF4 in cell proliferation. Cancer Survey 27: 293–310.

Gallie DR (2002) The 5′‐leader of tobacco mosaic virus promotes translation through enhanced recruitment of eIF4F. Nucleic Acids Research 30: 3401–3411.

Gao W, Tyagi S, Kramer FR and Goldman E (1997) Messenger RNA release from ribosomes during 5′‐translational blockage by consecutive low‐usage arginine but not leucine codons in E. coli. Molecular Microbiology 25: 707–716. Erratum: (1998) 27: 669.

Geballe AP and Morris DR (1994) Initiation codons within 5′‐leaders of mRNAs as regulators of translation. Trends in Biochemical Science 19: 159–164.

Gerdes K, Gultyaev AP, Franch T, Pedersen K and Mikkelsen ND (1997) Antisense RNA‐regulated programmed cell death. Annual Review of Genetics 31: 1–31.

Golshani A, Golomehova V, Mironova R, Ivanov IG and AbouHaidar MG (1997) Does the epsilon sequence of phage T7 function as an initiator for the translation of CAT mRNA in E. coli? Biochemical and Biophysical Research Communications 236: 253–256.

Gottesman S (2004) The small RNA regulators of E. coli: roles and mechanisms. Annual Review of Microbiology 58: 303–328.

Hammer BK and Bassler BL (2007) Regulatory small RNAs circumvent the conventional quorum sensing pathway in pandemic Vibrio cholerae. Proceedings of the National Academy of Sciences of the USA 104: 11145–11149.

He L, Soderbom F, Wagner EG et al. (1993) PcnB is required for the rapid degradation of RNAi, the antisense RNA that controls the copy number of ColE1‐related plasmids. Molecular Microbiology 9: 1131–1142.

Hui A, Hayflick J, Dinkelspiel K and de Boer HA (1984) Mutagenesis of the three bases preceding the start codon of the beta‐galactosidase mRNA and its effect on translation in E. coli. EMBO Journal 3: 623–629.

Ito K, Kawakami K and Nakamura Y (1993) Multiple control of E. coli lysyl‐tRNA synthetase expression involves a transcriptional repressor and a translational enhancer element. Proceedings of the National Academy of Sciences of the USA 90: 302–306.

Ivey‐Hoyle M and Steege DA (1992) Mutational analysis of an inherently defective translation initiation site. Journal of Molecular Biology 224: 1039–1054.

Jin X, Turcott E, Englehardt S, Mize GJ and Morris DR (2003) The two upstream open reading frames of oncogene mdm2 have different translational regulatory properties. Journal of Biological Chemistry 278: 25716–25721.

Joanny G, Le Derout J, Bréchemier‐Baey D et al. (2007) Polyadenylation of a functional mRNA controls gene expression in E. coli. Nucleic Acids Research 35: 2494–2502.

Kane JF (1995) Effects of rare codon clusters on high‐level expression of heterologous proteins in E. coli. Current Opinion in Biotechnology 6: 494–500.

Kozak M (1989) Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs. Molecular Cell Biology 9: 5134–5142.

Liebhaber SA, Cash F and Eshleman SS (1992) Translation inhibition by an mRNA coding region secondary structure is determined by its proximity to the AUG initiation codon. Journal of Molecular Biology 226: 609–621.

Lodish HF and Robertson HD (1969) Regulation of in vitro translation of bacteriophage f2 RNA. Cold Spring Harbor Symposia on Quantitative Biology 34: 655–673.

Lovett PS (1996) Translation attenuation regulation of chloramphenicol resistance in bacteria – a review. Gene 179: 157–162.

Ma C and Simons RW (1990) The IS10 antisense RNA blocks ribosome binding at the transposase translation initiation site. EMBO Journal 9: 1267–1274.

Ma CK, Kolesnikow T, Rayner JC et al. (1994) Control of translation by mRNA secondary structure: the importance of the kinetics of structure formation. Molecular Microbiology 14: 1033–1047.

Macdonald PM, Kutter E and Mosig G (1984) Regulation of a bacteriophage T4 late gene, soc, which maps in an early region. Genetics 106: 17–27.

Martin SE and Caplen NJ (2007) Applications of RNA interference in mammalian systems. Annual Review of Genomics and Human Genetics 8: 81–108.

Matteson RJ, Biswas SJ and Steege DA (1991) Distinctive patterns of translational reinitiation in the lac repressor mRNA: bridging of long distances by out‐of‐frame translation and RNA secondary structure, effects of primary sequence. Nucleic Acids Research 19: 3499–3506.

Mattheakis L, Vu L, Sor F and Nomura M (1989) Retroregulation of the synthesis of ribosomal proteins L14 and L24 by feedback repressor S8 in E. coli. Proceedings of the National Academy of Sciences of the USA 86: 448–452.

McPheeters DS, Christensen A, Young ET, Stormo G and Gold L (1986) Translational regulation of expression of the bacteriophage T4 lysozyme gene. Nucleic Acids Research 14: 5813–5826.

Min Jou W, Haegeman G, Ysebaert M and Fiers W (1972) Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein. Nature 237: 82–88.

Morita M, Kanemori M, Yanagi H and Yura T (1999a) Heat‐induced synthesis of sigma32 in E. coli: structural and functional dissection of rpoH mRNA secondary structure. Journal of Bacteriology 181: 401–410.

Morita MT, Tanaka Y, Kodama TS et al. (1999b) Translational induction of heat shock transcription factor sigma32: evidence for a built‐in RNA thermosensor. Genes & Development 13: 655–665.

Nakatogawa H, Murakami A and Ito K (2004) Control of SecA and SecM translation by protein secretion. Current Opinion in Microbiology 7: 145–150.

Nivinskas R, Malys N, Klausa V, Vaiskunaite R and Gineikiene E (1999) Post‐transcriptional control of bacteriophage T4 gene 25 expression: mRNA secondary structure that enhances translational initiation. Journal of Molecular Biology 288: 291–304.

O'Connor M, Asai T, Squires CL and Dahlberg AE (1999) Enhancement of translation by the downstream box does not involve base pairing of mRNA with the penultimate stem sequence of 16S rRNA. Proceedings of the National Academy of Sciences of the USA 96: 8973–8978.

O'Connor M and Dahlberg AE (2001) Enhancement of translation by the epsilon element is independent of the sequence of the 460 region of 16S rRNA. Nucleic Acids Research 29: 1420–1425.

Olins PO and Rangwala SH (1989) A novel sequence element derived from bacteriophage T7 mRNA acts as an enhancer of translation of the lacZ gene in E. coli. Journal of Biological Chemistry 264: 16973–16976.

Peabody DS (1993) The RNA binding site of bacteriophage MS2 coat protein. EMBO Journal 12: 595–600.

Rex G, Surin B, Besse G, Schneppe B and McCarthy JE (1994) The mechanism of translational coupling in E. coli. Higher order structure in the atpHA mRNA acts as a conformational switch regulating the access of de novo initiating ribosomes. Journal of Biological Chemistry 269: 18118–18127.

Rojiani M and Goldman E (1986) Dependence of MS2 and T4 phage growth upon host amino acid biosynthesis during infections of E. coli. Virology 150: 313–317.

Saito K, Mattheakis LC and Nomura M (1994) Post‐transcriptional regulation of the str operon in E. coli. Ribosomal protein S7 inhibits coupled translation of S7 but not its independent translation. Journal of Molecular Biology 235: 111–124.

Satchidanandam V and Shivashankar Y (1997) Availability of a second upstream AUG can completely overcome inhibition of protein synthesis initiation engendered by mRNA secondary structure encompassing the start codon. Gene 196: 231–237.

Schmeissner U, McKenney K, Rosenberg M and Court D (1984) Removal of a terminator structure by RNA processing regulates int gene expression. Journal of Molecular Biology 176: 39–53.

Schulz VP and Reznikoff WS (1990) In vitro secondary structure analysis of mRNA from lacZ translation initiation mutants. Journal of Molecular Biology 211: 427–445.

Schulz VP and Reznikoff WS (1991) Translation initiation of IS50R read‐through transcripts. Journal of Molecular Biology 221: 65–80.

Sengupta DJ, Wickens M and Fields S (1999) Identification of RNAs that bind to a specific protein using the yeast three‐hybrid system. RNA 5: 596–601.

Sor F, Bolotin‐Fukuhara M and Nomura M (1987) Mutational alterations of translational coupling in the L11 ribosomal protein operon of E. coli. Journal of Bacteriology 169: 3495–3507.

Sprengart ML, Fuchs E and Porter AG (1996) The downstream box: an efficient and independent translation initiation signal in E. coli. EMBO Journal 15: 665–674.

Strome S and Young ET (1980) Translational discrimination against bacteriophage T7 gene 0.3 messenger RNA. Journal of Molecular Biology 136: 433–450.

Thomas LK, Dix DB and Thompson RC (1988) Codon choice and gene expression: synonymous codons differ in their ability to direct aminoacylated‐transfer RNA binding to ribosomes in vitro. Proceedings of the National Academy of Sciences of the USA 85: 4242–4246.

Tu KC and Bassler BL (2007) Multiple small RNAs act additively to integrate sensory information and control quorum sensing in Vibrio harveyi. Genes & Developments 21: 221–233.

van Himbergen J, van Geffen B and van Duin J (1993) Translational control by a long range RNA‐RNA interaction; a basepair substitution analysis. Nucleic Acids Research 21: 1713–1717.

Wakita T, Moradpour D, Tokushihge K and Wands JR (1999) Antiviral effects of antisense RNA on hepatitis C virus RNA translation and expression. Journal of Medical Virology 57: 217–222.

Wikstrom PM, Lind LK, Berg DE and Bjork GR (1992) Importance of mRNA folding and start codon accessibility in the expression of genes in a ribosomal protein operon of E. coli. Journal of Molecualr Biology 224: 949–966.

Yasueda H, Takechi S, Sugiyama T and Itoh T (1994) Control of ColE2 plasmid replication: negative regulation of the expression of the plasmid‐specified initiator protein, Rep, at a posttranscriptional step. Molecular & General Genetics 244: 41–48.

Yoshida T, Qin L, Egger LA and Inouye M (2006) Transcription regulation of ompF and ompC by a single transcription factor, OmpR. Journal of Biological Chemistry 281: 17114–17123.

Zahn K and Landy A (1996) Modulation of lambda integrase synthesis by rare arginine tRNA. Molecular Microbiology 21: 69–76.

Zhang J and Deutscher MP (1992) A uridine‐rich sequence required for translation of prokaryotic mRNA. Proceedings of the National Academy of Sciences of the USA 89: 2605–2609.

Zhang SP, Zubay G and Goldman E (1991) Low‐usage codons in E. coli, yeast, fruit fly and primates. Gene 105: 61–72.

Further Reading

de Smit MH and van Duin J (1990) Control of prokaryotic translational initiation by mRNA secondary structure. Progress in Nucleic Acid Research and Molecular Biology 38: 1–35.

Deutscher MP (2006) Degradation of RNA in bacteria: comparison of mRNA and stable RNA. Nucleic Acids Research 34: 659–666.

Hershey JWB, Mathews MB and Sonenberg N (eds) (1996) Translational Control. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Jackson RJ (2005) Alternative mechanisms of initiating translation of mammalian mRNAs. Biochemical Society Transactions 33: 1231–1241.

Lindahl L and Hinnebusch A (1992) Diversity of mechanisms in the regulation of translation in prokaryotes and lower eukaryotes. Current Opinion in Genetics and Development 2: 720–726.

Lodish HF (1976) Translational control of protein synthesis. Annual Review of Biochemistry 45: 39–72.

McCarthy JE and Gualerzi C (1990) Translational control of prokaryotic gene expression. Trends in Genetics 6: 78–85.

Rana TM (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nature Reviews. Molecular Cell Biology 8: 23–36.

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

Storz G, Altuvia S and Wassarman KM (2005) An abundance of RNA regulators. Annual Review of Biochemistry 74: 199–217.

Wagner EG and Simons RW (1994) Antisense RNA control in bacteria, phages, and plasmids. Annual Review of Microbiology 48: 713–742.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Goldman, Emanuel(Dec 2008) Translation Control by RNA. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000859.pub2]