A wobble base pair is a pairing between two nucleotides in RNA molecules that does not follow Watson-Crick base pair rules.[1] The four main wobble base pairs are guanine-uracil (G-U), hypoxanthine-uracil (I-U), hypoxanthine-adenine (I-A), and hypoxanthine-cytosine (I-C). In order to maintain consistency of nucleic acid nomenclature, "I" is used for hypoxanthine because hypoxanthine is the nucleobase of inosine;[2] nomenclature otherwise follows the names of nucleobases and their corresponding nucleosides (e.g., "G" for both guanine and guanosine – as well as for deoxyguanosine). The thermodynamic stability of a wobble base pair is comparable to that of a Watson-Crick base pair. Wobble base pairs are fundamental in RNA secondary structure and are critical for the proper translation of the genetic code.
In the genetic code, there are 43 = 64 possible codons (3 nucleotide sequences). For translation, each of these codons requires a tRNA molecule with an anticodon with which it can stably complement. If each tRNA molecule is paired with its complementary mRNA codon using canonical Watson-Crick base pairing, then 64 types of tRNA molecule would be required. In the standard genetic code, three of these 64 mRNA codons (UAA, UAG and UGA) are stop codons. These terminate translation by binding to release factors rather than tRNA molecules, so canonical pairing would require 61 species of tRNA. Since most organisms have fewer than 45 types of tRNA, [3] some tRNA types can pair with multiple, synonymous codons, all of which encode the same amino acid. In 1966, Francis Crick proposed the Wobble Hypothesis to account for this. He postulated that the 5' base on the anticodon, which binds to the 3' base on the mRNA, was not as spatially confined as the other two bases and could, thus, have non-standard base pairing.[4] Crick creatively named it for the small amount of "play" or wobble that occurs at this third codon position. Movement ("wobble") of the base in the 5' anticodon position is necessary for small conformational adjustments that affect the overall pairing geometry of anticodons of tRNA.[5][6]
As an example, yeast tRNAPhe has the anticodon 5'-GmAA-3' and can recognize the codons 5'-UUC-3' and 5'-UUU-3'. It is, therefore, possible for non-Watson–Crick base pairing to occur at the third codon position, i.e., the 3' nucleotide of the mRNA codon and the 5' nucleotide of the tRNA anticodon.[7]
Wobble hypothesisedit
These notions led Francis Crick to the creation of the wobble hypothesis, a set of four relationships explaining these naturally occurring attributes.
The first two bases in the codon create the coding specificity, for they form strong Watson-Crick base pairs and bond strongly to the anticodon of the tRNA.
When reading 5' to 3' the first nucleotide in the anticodon (which is on the tRNA and pairs with the last nucleotide of the codon on the mRNA) determines how many nucleotides the tRNA actually distinguishes. If the first nucleotide in the anticodon is a C or an A, pairing is specific and acknowledges original Watson-Crick pairing, that is: only one specific codon can be paired to that tRNA. If the first nucleotide is U or G, the pairing is less specific and in fact two bases can be interchangeably recognized by the tRNA. Inosine displays the true qualities of wobble, in that if that is the first nucleotide in the anticodon, any of three bases in the original codon can be matched with the tRNA.
Due to the specificity inherent in the first two nucleotides of the codon, if one amino acid is coded for by multiple anticodons and those anticodons differ in either the second or third position (first or second position in the codon) then a different tRNA is required for that anticodon.
The minimum requirement to satisfy all possible codons (61 excluding three stop codons) is 32 tRNAs. That is 31 tRNAs for the amino acids and one initiation codon.[8]
tRNA base pairing schemesedit
Wobble pairing rules. Watson-Crick base pairs are shown in bold. Parentheses denote bindings that work but will be favoured less. A leading x denotes derivatives (in general) of the base that follows.
Aside from the necessity of wobble, that our cells have a limited amount of tRNAs and wobble allows for more flexibility, wobble base pairs have been shown to facilitate many biological functions, most clearly demonstrated in the bacterium Escherichia coli, a model organism. In fact, in a study of E. coli's tRNA for alanine there is a wobble base pair that determines whether the tRNA will be aminoacylated. When a tRNA reaches an aminoacyl tRNA synthetase, the job of the synthetase is to join the t-shaped RNA with its amino acid. These aminoacylated tRNAs go on to the translation of an mRNA transcript, and are the fundamental elements that connect to the codon of the amino acid.[1] The necessity of the wobble base pair is illustrated through experimentation where the Guanine-Uracil pairing is changed to its natural Guanine-Cytosine pairing. Oligoribonucleotides were synthesized on a Gene Assembler Plus, and then spread across a DNA sequence known to code a tRNA for alanine, 2D-NMRs are then run on the products of these new tRNAs and compared to the wobble tRNAs. The results indicate that with that wobble base pair changed, structure is also changed and an alpha helix can no longer be formed. The alpha helix was the recognizable structure for the aminoacyl tRNA synthetase and thus the synthetase does not connect the amino acid alanine with the tRNA for alanine. This wobble base pairing is essential for the use of the amino acid alanine in E. coli and its significance here would imply significance in many related species.[10] More information can be seen on aminoacyl tRNA synthetase and the genomes of E. coli tRNA at the External links, Information on Aminoacyl tRNA Synthetases and Genomic tRNA Database.
^These relationships can be further observed, as well as full codons and anticodons in the correct reading frame at: SBDR (2008-04-15). "Genetic Code and Amino Acid Translation". Society for Biomedical Diabetes Research. from the original on 2014-11-04. Retrieved 2014-09-14. For a modern view on the pairings, see doi:10.1093/nar/gkh185.
Referencesedit
^ abCampbell, Neil; Reece, Jane B. (2011). Biology (9th ed.). Boston: Benjamin Cummings. pp. 339–342. ISBN978-0321558237.
^Kuchin, Sergei (19 May 2011). . Journal of Microbiology & Biology Education. 12 (1): 64–66. doi:10.1128/jmbe.v12i1.267. PMC3577215. PMID 23653747. Archived from the original on 17 October 2013. The correct name of the base in inosine (which is a nucleoside) is hypoxanthine, however, for consistency with the nucleic acid nomenclature, the shorthand [I] is more appropriate...
^Lowe, Todd; Chan, Patricia (18 April 2011). "Genomic tRNA Database". University of California, Santa Cruz. from the original on 30 May 2015. Retrieved 31 October 2015.
^Crick, F.H.C. (August 1966). "Codon—anticodon pairing: The wobble hypothesis" (PDF). Journal of Molecular Biology. 19 (2): 548–555. CiteSeerX10.1.1.693.2333. doi:10.1016/S0022-2836(66)80022-0. PMID 5969078. (PDF) from the original on 4 March 2016. Retrieved 31 October 2015.
^Mathews, Christopher K.; Van Holde, K.E.; Appling, Dean; et al., eds. (2012). Biochemistry (4th ed.). Toronto: Prentice Hall. p. 1181. ISBN978-0-13-800464-4.
^Voet, Donald; Voet, Judith (2011). Biochemistry (4th ed.). Hoboken, NJ: John Wiley & Sons. pp. 1360–1361. ISBN9780470570951.
^Varani, Gabriele; McClain, William H (July 2000). "The G·U wobble base pair". EMBO Reports. 1 (1): 18–23. doi:10.1093/embo-reports/kvd001. PMC1083677. PMID 11256617.
^Cox, Michael M.; Nelson, David L. (2013). "Protein Metabolism: Wobble Allows Some tRNA's to Recognize More than One Codon". Lehninger Principles of Biochemistry (6th ed.). New York: W.H. Freeman. pp. 1108–1110. ISBN9780716771081. Retrieved 31 October 2015.
^Murphy IV, Frank V; Ramakrishnan, V (21 November 2004). "Structure of a purine-purine wobble base pair in the decoding center of the ribosome". Nature Structural & Molecular Biology. 11 (12): 1251–1252. doi:10.1038/nsmb866. PMID 15558050. S2CID 27022506.
^Limmer, S.; Reif, B.; Ott, G.; Arnold, L.; Sprinzl, M. (1996). "NMR evidence for helix geometry modifications by a G-U wobble base pair in the acceptor arm of E. Coli tRNA(Ala)". FEBS Letters. 385 (1–2): 15–20. doi:10.1016/0014-5793(96)00339-0. PMID 8641457.
External linksedit
tRNA, the Adaptor Hypothesis and the Wobble Hypothesis
Wobble base-pairing between codons and anticodons
Genetic Code and Amino Acid Translation
Information of Aminoacyl tRNA Synthetases
Genomic tRNA Database
April 12, 2024
wobble, base, pair, wobble, base, pair, pairing, between, nucleotides, molecules, that, does, follow, watson, crick, base, pair, rules, four, main, wobble, base, pairs, guanine, uracil, hypoxanthine, uracil, hypoxanthine, adenine, hypoxanthine, cytosine, order. A wobble base pair is a pairing between two nucleotides in RNA molecules that does not follow Watson Crick base pair rules 1 The four main wobble base pairs are guanine uracil G U hypoxanthine uracil I U hypoxanthine adenine I A and hypoxanthine cytosine I C In order to maintain consistency of nucleic acid nomenclature I is used for hypoxanthine because hypoxanthine is the nucleobase of inosine 2 nomenclature otherwise follows the names of nucleobases and their corresponding nucleosides e g G for both guanine and guanosine as well as for deoxyguanosine The thermodynamic stability of a wobble base pair is comparable to that of a Watson Crick base pair Wobble base pairs are fundamental in RNA secondary structure and are critical for the proper translation of the genetic code Wobble base pairs for inosine and guanine Contents 1 Brief history 1 1 Wobble hypothesis 1 2 tRNA base pairing schemes 2 Biological importance 3 See also 4 Footnotes 5 References 6 External linksBrief history editIn the genetic code there are 43 64 possible codons 3 nucleotide sequences For translation each of these codons requires a tRNA molecule with an anticodon with which it can stably complement If each tRNA molecule is paired with its complementary mRNA codon using canonical Watson Crick base pairing then 64 types of tRNA molecule would be required In the standard genetic code three of these 64 mRNA codons UAA UAG and UGA are stop codons These terminate translation by binding to release factors rather than tRNA molecules so canonical pairing would require 61 species of tRNA Since most organisms have fewer than 45 types of tRNA 3 some tRNA types can pair with multiple synonymous codons all of which encode the same amino acid In 1966 Francis Crick proposed the Wobble Hypothesis to account for this He postulated that the 5 base on the anticodon which binds to the 3 base on the mRNA was not as spatially confined as the other two bases and could thus have non standard base pairing 4 Crick creatively named it for the small amount of play or wobble that occurs at this third codon position Movement wobble of the base in the 5 anticodon position is necessary for small conformational adjustments that affect the overall pairing geometry of anticodons of tRNA 5 6 As an example yeast tRNAPhe has the anticodon 5 GmAA 3 and can recognize the codons 5 UUC 3 and 5 UUU 3 It is therefore possible for non Watson Crick base pairing to occur at the third codon position i e the 3 nucleotide of the mRNA codon and the 5 nucleotide of the tRNA anticodon 7 Wobble hypothesis edit These notions led Francis Crick to the creation of the wobble hypothesis a set of four relationships explaining these naturally occurring attributes The first two bases in the codon create the coding specificity for they form strong Watson Crick base pairs and bond strongly to the anticodon of the tRNA When reading 5 to 3 the first nucleotide in the anticodon which is on the tRNA and pairs with the last nucleotide of the codon on the mRNA determines how many nucleotides the tRNA actually distinguishes If the first nucleotide in the anticodon is a C or an A pairing is specific and acknowledges original Watson Crick pairing that is only one specific codon can be paired to that tRNA If the first nucleotide is U or G the pairing is less specific and in fact two bases can be interchangeably recognized by the tRNA Inosine displays the true qualities of wobble in that if that is the first nucleotide in the anticodon any of three bases in the original codon can be matched with the tRNA Due to the specificity inherent in the first two nucleotides of the codon if one amino acid is coded for by multiple anticodons and those anticodons differ in either the second or third position first or second position in the codon then a different tRNA is required for that anticodon The minimum requirement to satisfy all possible codons 61 excluding three stop codons is 32 tRNAs That is 31 tRNAs for the amino acids and one initiation codon 8 tRNA base pairing schemes edit Wobble pairing rules Watson Crick base pairs are shown in bold Parentheses denote bindings that work but will be favoured less A leading x denotes derivatives in general of the base that follows tRNA 5 anticodon base mRNA 3 codon base Crick note 1 mRNA 3 codon base Revised 9 A U U C G or A C G GG C or U C or UU A or G A G U or C I A C or U A C or Uk2C Axm5s2U xm5Um Um xm5U A or G xo5U U A or GBiological importance editAside from the necessity of wobble that our cells have a limited amount of tRNAs and wobble allows for more flexibility wobble base pairs have been shown to facilitate many biological functions most clearly demonstrated in the bacterium Escherichia coli a model organism In fact in a study of E coli s tRNA for alanine there is a wobble base pair that determines whether the tRNA will be aminoacylated When a tRNA reaches an aminoacyl tRNA synthetase the job of the synthetase is to join the t shaped RNA with its amino acid These aminoacylated tRNAs go on to the translation of an mRNA transcript and are the fundamental elements that connect to the codon of the amino acid 1 The necessity of the wobble base pair is illustrated through experimentation where the Guanine Uracil pairing is changed to its natural Guanine Cytosine pairing Oligoribonucleotides were synthesized on a Gene Assembler Plus and then spread across a DNA sequence known to code a tRNA for alanine 2D NMRs are then run on the products of these new tRNAs and compared to the wobble tRNAs The results indicate that with that wobble base pair changed structure is also changed and an alpha helix can no longer be formed The alpha helix was the recognizable structure for the aminoacyl tRNA synthetase and thus the synthetase does not connect the amino acid alanine with the tRNA for alanine This wobble base pairing is essential for the use of the amino acid alanine in E coli and its significance here would imply significance in many related species 10 More information can be seen on aminoacyl tRNA synthetase and the genomes of E coli tRNA at the External links Information on Aminoacyl tRNA Synthetases and Genomic tRNA Database See also editBase pair Hoogsteen base pair Synonymous substitutionFootnotes edit These relationships can be further observed as well as full codons and anticodons in the correct reading frame at SBDR 2008 04 15 Genetic Code and Amino Acid Translation Society for Biomedical Diabetes Research Archived from the original on 2014 11 04 Retrieved 2014 09 14 For a modern view on the pairings see doi 10 1093 nar gkh185 References edit a b Campbell Neil Reece Jane B 2011 Biology 9th ed Boston Benjamin Cummings pp 339 342 ISBN 978 0321558237 Kuchin Sergei 19 May 2011 Covering All the Bases in Genetics Simple Shorthands and Diagrams for Teaching Base Pairing to Biology Undergraduates Journal of Microbiology amp Biology Education 12 1 64 66 doi 10 1128 jmbe v12i1 267 PMC 3577215 PMID 23653747 Archived from the original on 17 October 2013 The correct name of the base in inosine which is a nucleoside is hypoxanthine however for consistency with the nucleic acid nomenclature the shorthand I is more appropriate Lowe Todd Chan Patricia 18 April 2011 Genomic tRNA Database University of California Santa Cruz Archived from the original on 30 May 2015 Retrieved 31 October 2015 Crick F H C August 1966 Codon anticodon pairing The wobble hypothesis PDF Journal of Molecular Biology 19 2 548 555 CiteSeerX 10 1 1 693 2333 doi 10 1016 S0022 2836 66 80022 0 PMID 5969078 Archived PDF from the original on 4 March 2016 Retrieved 31 October 2015 Mathews Christopher K Van Holde K E Appling Dean et al eds 2012 Biochemistry 4th ed Toronto Prentice Hall p 1181 ISBN 978 0 13 800464 4 Voet Donald Voet Judith 2011 Biochemistry 4th ed Hoboken NJ John Wiley amp Sons pp 1360 1361 ISBN 9780470570951 Varani Gabriele McClain William H July 2000 The G U wobble base pair EMBO Reports 1 1 18 23 doi 10 1093 embo reports kvd001 PMC 1083677 PMID 11256617 Cox Michael M Nelson David L 2013 Protein Metabolism Wobble Allows Some tRNA s to Recognize More than One Codon Lehninger Principles of Biochemistry 6th ed New York W H Freeman pp 1108 1110 ISBN 9780716771081 Retrieved 31 October 2015 Murphy IV Frank V Ramakrishnan V 21 November 2004 Structure of a purine purine wobble base pair in the decoding center of the ribosome Nature Structural amp Molecular Biology 11 12 1251 1252 doi 10 1038 nsmb866 PMID 15558050 S2CID 27022506 Limmer S Reif B Ott G Arnold L Sprinzl M 1996 NMR evidence for helix geometry modifications by a G U wobble base pair in the acceptor arm of E Coli tRNA Ala FEBS Letters 385 1 2 15 20 doi 10 1016 0014 5793 96 00339 0 PMID 8641457 External links edittRNA the Adaptor Hypothesis and the Wobble Hypothesis Wobble base pairing between codons and anticodons Genetic Code and Amino Acid Translation Information of Aminoacyl tRNA Synthetases Genomic tRNA Database Retrieved from https en wikipedia org w index php title Wobble base pair amp oldid 1106547019, wikipedia, wiki, book, books, library,
