Nonsense suppressor: Difference between revisions

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Nonsense suppressors change the effects of nonsense mutations by altering how stop codons are read.  The largest class of nonsense suppressors are mutations in [[:Category:tRNA genes]] that alter the codon-anticodon interaction to allow a stop codon to be read by that tRNA.  This will only suppress the mutation if the amino acid inserted restores a functional protein product.
Nonsense suppressors change the effects of nonsense mutations by altering how stop codons are read.  The largest class of nonsense suppressors are mutations in [[:Category:tRNA genes]] that alter the codon-anticodon interaction to allow a stop codon to be read by that tRNA.  This will only suppress the mutation if the amino acid inserted restores a functional protein product.
Nonsense suppression is defined genetically based on reversing an observable phenotype.  Note that this does not mean full restoration of normal function.  Nonsense suppression is often incomplete ("leaky") and [[wikipedia:Pleiotropy|pleiotropic]].


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{| {{Prettytable}} id="F46b4cf5d3f9bd"  class=" tableEdit " 
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!gene!!synonyms!!tRNA affected!!aa inserted!!codons recognized
!|gene!!synonyms!!tRNA affected!!aa inserted!!codons recognized
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[[serU]], [[serV]]
[[serU]], [[serV]]
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supD, supH, su1, Su-1, SuI, ftsM, su_1
supD, supH, su1, Su-1, SuI, ftsM, su_1
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|
[[tRNA-Ser(CGA) (Serine tRNA2)| tRNA<sup>Ser</sup>(CGA) (Serine tRNA2)]]
tRNA-Ser(CGA) (Serine tRNA2)| tRNA<sup>Ser</sup>(CGA) (Serine tRNA2)
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Serine <ref name='PMID:14337506'/>
Serine <ref name='PMID:14337506'/>
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Amber  
Amber  
|-
|-  
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[[glnX]], [[glnV]]
[[glnX]], [[glnV]]
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supE, Su2, Su_II
supE, Su2, Su_II
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[[tRNA-Gln(CUG) (Glutamine tRNA2)|tRNA<sup>Gln</sup>(CUG) (Glutamine tRNA2)]]
tRNA-Gln(CUG) (Glutamine tRNA2)|tRNA<sup>Gln</sup>(CUG) (Glutamine tRNA2)
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Glutamine<ref name='PMID:4286570'/>
Glutamine<ref name='PMID:4286570'/>
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Amber  
Amber  
|-
|-  
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[[tyrT]]
[[tyrT]]
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supF
supF
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[[tRNA-Tyr(GUA) (Tyrosine tRNA1)|tRNA<sup>Tyr</sup>(GUA) (Tyrosine tRNA1)]]
tRNA-Tyr(GUA) (Tyrosine tRNA1)|tRNA<sup>Tyr</sup>(GUA) (Tyrosine tRNA1)
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Tyrosine<ref name='PMID:4286570'/>
Tyrosine<ref name='PMID:4286570'/>
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Amber  
Amber  
|-
|-  
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[[lysT]]
[[lysT]]
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supG, supK, supL, Su(beta), su-5,
supG, supK, supL, Su(beta), su-5,
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[[tRNA-Lys(UUU) (Lysine tRNA)|tRNA<sup>Lys</sup>(UUU) (Lysine tRNA)]]
tRNA-Lys(UUU) (Lysine tRNA)|tRNA<sup>Lys</sup>(UUU) (Lysine tRNA)
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Lysine
Lysine
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Ochre  
Ochre  
|-
|-  
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[[leuX]]
[[leuX]]
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supP, Su-6
supP, Su-6
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[[tRNA-Leu(CAA) (Leucine tRNA5)|tRNA<sup>Leu</sup>(CAA) (Leucine tRNA5)]]
tRNA-Leu(CAA) (Leucine tRNA5)|tRNA<sup>Leu</sup>(CAA) (Leucine tRNA5)
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Leucine
Leucine
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Amber  
Amber  
|-
|-  
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[[tyrT]]
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supC
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[[tRNA-Tyr(GUA) (Tyrosine tRNA1)|tRNA<sup>Tyr</sup>(GUA) (Tyrosine tRNA1)]]
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Tyrosine<ref name='PMID:4286570'/>
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Ochre
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[[trpT]]
[[trpT]]
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supU, supV, su9
supU, supV, su9
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[[tRNA-Trp(CCA) (Tryptophan tRNA)|tRNA<sup>Trp</sup>(CCA) (Tryptophan tRNA)]]
tRNA-Trp(CCA) (Tryptophan tRNA)|tRNA<sup>Trp</sup>(CCA) (Tryptophan tRNA)
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Tryptophan
Tryptophan
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Opal  
Opal  
|-
|-  
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[[tyrU]]
[[tyrU]]
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supZ
supZ
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[[tRNA-Tyr(GUA) (Tyrosine tRNA2)|tRNA<sup>Tyr</sup>(GUA) (Tyrosine tRNA2)]]
tRNA-Tyr(GUA) (Tyrosine tRNA2)|tRNA<sup>Tyr</sup>(GUA) (Tyrosine tRNA2)
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Tyrosine
Tyrosine
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Amber  
Amber  
|-
|-  
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[[glnU]]
[[glnU]]
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supB
supB
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[[tRNA-Gln(UUG) (Glutamine tRNA1)|tRNA<sup>Gln</sup>(UUG) (Glutamine tRNA1)]]
tRNA-Gln(UUG) (Glutamine tRNA1)|tRNA<sup>Gln</sup>(UUG) (Glutamine tRNA1)
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Glutamine
Glutamine
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Ochre  
Ochre  
|-
|-  
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[[lysT]]
[[lysT]]
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supL
supL
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[[tRNA-Lys(UUU) (Lysine tRNA)|tRNA<sup>Lys</sup>(UUU) (Lysine tRNA)]]
tRNA-Lys(UUU) (Lysine tRNA)|tRNA<sup>Lys</sup>(UUU) (Lysine tRNA)
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Lysine
Lysine
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|
Ochre  
Ochre  
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<small>This table is incomplete and may have inaccuracies in the synonym lists for amber vs ochre.  Need to add the engineered suppressors from Kleina et al<ref name='PMID: 2193162'/> and Normanly et al<ref name='PMID: 2141650'/>.  Others?</small>
== tRNA suppressors ==
tRNA suppressors are often, but not always <ref>citation needed</ref>, caused by changes in the anticodon loop of the tRNA to allow recognition of a stop codon.  Due to wobble rules, amber suppressors are specific for amber (UAG) codons, while ochre suppressors recognize both Ochre (UAA) and Amber (UAG) codons via G=U and A=U basepairing.  The suppressor tRNA is no longer able to recognize its cognate codons, which means that in order to be viable, suppressor strains need to have another tRNA that recognizes the unmutated codons.  This can be accomplished using strains that are merodiploid for tRNAs that are present in single copy in ''E. coli'', or through the use of multicopy plasmids expressing the suppressor tRNA.
Because the suppressor tRNA is in competition with translation termination factors, the efficiency of suppression is usually less than 100%.  In general, ochre suppressors are less efficient than amber suppressors; this is probably due to selection for suppressors that can survive the pleiotropic effects of widespread translational readthrough.  Because more ''E. coli'' genes terminate in UAA than UAG, amber suppressors tend to be less sickly than ochre suppressors.
== non-tRNA nonsense suppressors ==
UGA suppressors have been isolated<ref name = 'PMID: 2198904'/> in [[prfB]], which encodes peptide release factor RF2.
== See Also ==
== See Also ==
* [http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/rev-sup/nonsense-suppressors.html http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/rev-sup/nonsense-suppressors.html] Stan Maloy's page on nonsense suppressors
* [http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/rev-sup/nonsense-suppressors.html http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/rev-sup/nonsense-suppressors.html] Stan Maloy's page on nonsense suppressors
== References ==
== References ==
<references/>
<references/>

Latest revision as of 07:24, 9 August 2011

Nonsense suppressors change the effects of nonsense mutations by altering how stop codons are read. The largest class of nonsense suppressors are mutations in Category:tRNA genes that alter the codon-anticodon interaction to allow a stop codon to be read by that tRNA. This will only suppress the mutation if the amino acid inserted restores a functional protein product.

Nonsense suppression is defined genetically based on reversing an observable phenotype. Note that this does not mean full restoration of normal function. Nonsense suppression is often incomplete ("leaky") and pleiotropic.

gene synonyms tRNA affected aa inserted codons recognized

serU, serV

supD, supH, su1, Su-1, SuI, ftsM, su_1

tRNA-Ser(CGA) (Serine tRNA2)| tRNASer(CGA) (Serine tRNA2)

Serine [1]

Amber

glnX, glnV

supE, Su2, Su_II

tRNA-Gln(CUG) (Glutamine tRNA2)|tRNAGln(CUG) (Glutamine tRNA2)

Glutamine[2]

Amber

tyrT

supF

tRNA-Tyr(GUA) (Tyrosine tRNA1)|tRNATyr(GUA) (Tyrosine tRNA1)

Tyrosine[2]

Amber

lysT

supG, supK, supL, Su(beta), su-5,

tRNA-Lys(UUU) (Lysine tRNA)|tRNALys(UUU) (Lysine tRNA)

Lysine

Ochre

leuX

supP, Su-6

tRNA-Leu(CAA) (Leucine tRNA5)|tRNALeu(CAA) (Leucine tRNA5)

Leucine

Amber

trpT

supU, supV, su9

tRNA-Trp(CCA) (Tryptophan tRNA)|tRNATrp(CCA) (Tryptophan tRNA)

Tryptophan

Opal

tyrU

supZ

tRNA-Tyr(GUA) (Tyrosine tRNA2)|tRNATyr(GUA) (Tyrosine tRNA2)

Tyrosine

Amber

glnU

supB

tRNA-Gln(UUG) (Glutamine tRNA1)|tRNAGln(UUG) (Glutamine tRNA1)

Glutamine

Ochre

lysT

supL

tRNA-Lys(UUU) (Lysine tRNA)|tRNALys(UUU) (Lysine tRNA)

Lysine

Ochre

edit table

This table is incomplete and may have inaccuracies in the synonym lists for amber vs ochre. Need to add the engineered suppressors from Kleina et al[3] and Normanly et al[4]. Others?

tRNA suppressors

tRNA suppressors are often, but not always [5], caused by changes in the anticodon loop of the tRNA to allow recognition of a stop codon. Due to wobble rules, amber suppressors are specific for amber (UAG) codons, while ochre suppressors recognize both Ochre (UAA) and Amber (UAG) codons via G=U and A=U basepairing. The suppressor tRNA is no longer able to recognize its cognate codons, which means that in order to be viable, suppressor strains need to have another tRNA that recognizes the unmutated codons. This can be accomplished using strains that are merodiploid for tRNAs that are present in single copy in E. coli, or through the use of multicopy plasmids expressing the suppressor tRNA.

Because the suppressor tRNA is in competition with translation termination factors, the efficiency of suppression is usually less than 100%. In general, ochre suppressors are less efficient than amber suppressors; this is probably due to selection for suppressors that can survive the pleiotropic effects of widespread translational readthrough. Because more E. coli genes terminate in UAA than UAG, amber suppressors tend to be less sickly than ochre suppressors.

non-tRNA nonsense suppressors

UGA suppressors have been isolated[6] in prfB, which encodes peptide release factor RF2.

See Also

References

  1. ↑ WEIGERT, MG & GAREN, A (1965) AMINO ACID SUBSTITUTIONS RESULTING FROM SUPPRESSION OF NONSENSE MUTATIONS. I. SERINE INSERTION BY THE SU-1 SUPPRESSOR GENE. J. Mol. Biol. 12 448-55 PubMed
  2. ↑ 2.0 2.1 Weigert, MG et al. (1965) Amino acid substitutions resulting from suppression of nonsense mutations. II. Glutamine insertion by the Su-2 gene; tyrosine insertion by the Su-3 gene. J. Mol. Biol. 14 522-7 PubMed
  3. ↑ Kleina, LG et al. (1990) Construction of Escherichia coli amber suppressor tRNA genes. II. Synthesis of additional tRNA genes and improvement of suppressor efficiency. J. Mol. Biol. 213 705-17 PubMed
  4. ↑ Normanly, J et al. (1990) Construction of Escherichia coli amber suppressor tRNA genes. III. Determination of tRNA specificity. J. Mol. Biol. 213 719-26 PubMed
  5. ↑ citation needed
  6. ↑ Chang, Z et al. (1990) Novel UGA-suppressors in Escherichia coli K-12. Jpn. J. Genet. 65 71-81 PubMed
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