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A release factor is a protein that allows for the termination of translation by recognizing the termination codon or stop codon in an mRNA sequence. They are named so because they release new peptides from the ribosome.

Peptide chain release factor, bacterial Class 1
Identifiers
SymbolPCRF
PfamPF03462
InterProIPR005139
Peptide chain release factor, bacterial Class 1, GGQ
Identifiers
SymbolRF-1
PfamPF00472
Pfam clanCL0337
InterProIPR000352
PROSITEPS00745

BackgroundEdit

During translation of mRNA, most codons are recognized by "charged" tRNA molecules, called aminoacyl-tRNAs because they are adhered to specific amino acids corresponding to each tRNA's anticodon. In the standard genetic code, there are three mRNA stop codons: UAG ("amber"), UAA ("ochre"), and UGA ("opal" or "umber"). Although these stop codons are triplets just like ordinary codons, they are not decoded by tRNAs. It was discovered by Mario Capecchi in 1967 that, instead, tRNAs do not ordinarily recognize stop codons at all, and that what he named "release factor" was not a tRNA molecule but a protein.[1] Later, it was demonstrated that different release factors recognize different stop codons.[2]

ClassificationEdit

There are two classes of release factors. Class 1 release factors recognize stop codons; they bind to the A site of the ribosome in a way mimicking that of tRNA, releasing the new polypeptide as it disassembles the ribosome.[3][4] Class 2 release factors are GTPases that enhance the activity of class 1 release factors. It helps the class 1 RF dissociate from the ribosome.[5]

Bacterial release factors include RF1, RF2, and RF3 (or PrfA, PrfB, PrfC in the "peptide release factor" gene nomenclature). RF1 and RF2 are class 1 RFs: RF1 recognizes UAA and UAG while RF2 recognizes UAA and UGA. RF3 is the class 2 release factor.[6] Eukaryotic and archaeal release factors are similar, with the naming changed to "eRF" for "eukaryotic release factor" and vice versa. a/eRF1 can recognize all three stop codons, while eRF3 (there is none known in archaea) works just like RF3.[6]

a/eRF1 (InterProIPR004403) show significant sequence similarity with their bacterial counterparts and are considered to form a separate family.[7] Bacterial RF3 are similar to EF-G while eukaryotic eRF3 is similar to eEF-1α.[8] In line with their symbiotic origin, eukaryotic mitochrondria and plastids use bacterial-type class I release factors.[9] As of April 2019, no definite reports of an organellar class II release factor can be found.

Human genesEdit

StructureEdit

Crystal structures have been solved for bacterial 70S ribosome bound to each of the three release factors, revealing details in codon recognition by RF1/2 and the EF-G-like rotation of EF3.[10] Cryo-EM structures have been obtained for eukaryotic mamallian 80S ribosome bound to eRF1 and/or eRF3, providing a view of structural rearrangements caused by the factors. Fitting the EM images to previously known crystal structures of individual parts provides identification and a more detailed view of the process.[11][12]

In both systems, (e)RF3 binds to the universal GTPase site on the ribosome.[10]

RF1/2Edit

a/eRF1Edit

RF3Edit

ReferencesEdit

  1. ^ Capecchi MR (September 1967). "Polypeptide chain termination in vitro: isolation of a release factor". Proceedings of the National Academy of Sciences of the United States of America. 58 (3): 1144–51. Bibcode:1967PNAS...58.1144C. doi:10.1073/pnas.58.3.1144. PMC 335760. PMID 5233840.
  2. ^ Scolnick E, Tompkins R, Caskey T, Nirenberg M (October 1968). "Release factors differing in specificity for terminator codons". Proceedings of the National Academy of Sciences of the United States of America. 61 (2): 768–74. Bibcode:1968PNAS...61..768S. doi:10.1073/pnas.61.2.768. PMC 225226. PMID 4879404.
  3. ^ Brown CM, Tate WP (December 1994). "Direct recognition of mRNA stop signals by Escherichia coli polypeptide chain release factor two". The Journal of Biological Chemistry. 269 (52): 33164–70. PMID 7806547.
  4. ^ Scarlett DJ, McCaughan KK, Wilson DN, Tate WP (April 2003). "Mapping functionally important motifs SPF and GGQ of the decoding release factor RF2 to the Escherichia coli ribosome by hydroxyl radical footprinting. Implications for macromolecular mimicry and structural changes in RF2". The Journal of Biological Chemistry. 278 (17): 15095–104. doi:10.1074/jbc.M211024200. PMID 12458201.
  5. ^ Jakobsen CG, Segaard TM, Jean-Jean O, Frolova L, Justesen J (2001). "[Identification of a novel termination release factor eRF3b expressing the eRF3 activity in vitro and in vivo]". Molekuliarnaia Biologiia. 35 (4): 672–81. PMID 11524954.
  6. ^ a b Weaver RF (2005). Molecular Biology. New York, NY: McGraw-Hill. pp. 616–621. ISBN 978-0-07-284611-9.
  7. ^ Buckingham RH, Grentzmann G, Kisselev L (May 1997). "Polypeptide chain release factors". Molecular Microbiology. 24 (3): 449–56. doi:10.1046/j.1365-2958.1997.3711734.x. PMID 9179839. Standard methods of sequence comparison do not show significant similarity between the prokaryotic factors RF1/2 and RF1
  8. ^ Inagaki Y, Ford Doolittle W (June 2000). "Evolution of the eukaryotic translation termination system: origins of release factors". Molecular Biology and Evolution. 17 (6): 882–9. doi:10.1093/oxfordjournals.molbev.a026368. PMID 10833194.
  9. ^ Duarte I, Nabuurs SB, Magno R, Huynen M (November 2012). "Evolution and diversification of the organellar release factor family". Molecular Biology and Evolution. 29 (11): 3497–512. doi:10.1093/molbev/mss157. PMC 3472500. PMID 22688947.
  10. ^ a b Zhou J, Korostelev A, Lancaster L, Noller HF (December 2012). "Crystal structures of 70S ribosomes bound to release factors RF1, RF2 and RF3". Current Opinion in Structural Biology. 22 (6): 733–42. doi:10.1016/j.sbi.2012.08.004. PMC 3982307. PMID 22999888.
  11. ^ Taylor D, Unbehaun A, Li W, Das S, Lei J, Liao HY, Grassucci RA, Pestova TV, Frank J (November 2012). "Cryo-EM structure of the mammalian eukaryotic release factor eRF1-eRF3-associated termination complex". Proceedings of the National Academy of Sciences of the United States of America. 109 (45): 18413–8. Bibcode:2012PNAS..10918413T. doi:10.1073/pnas.1216730109. PMC 3494903. PMID 23091004.
  12. ^ des Georges A, Hashem Y, Unbehaun A, Grassucci RA, Taylor D, Hellen CU, Pestova TV, Frank J (March 2014). "Structure of the mammalian ribosomal pre-termination complex associated with eRF1.eRF3.GDPNP". Nucleic Acids Research. 42 (5): 3409–18. doi:10.1093/nar/gkt1279. PMC 3950680. PMID 24335085.

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