Eukaryotic translation initiation (Homo sapiens)

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26, 271081214, 2029153-74, 5, 16-192822, 24, 25114, 5, 12, 143-5, 922, 243-5, 21-232812, 1326, 27cytosol40S ribosomal complexPABPeIF580S ribosomeGTPeIF4A subunits complexeIF5B:GDPeIF1AmRNPeIF5eIF143S: Ceruloplasmin mRNA:eIF4F:eIF4B:eIF4H:PABPeIF4Gphospho-L13a associated wth the 3' UTR GAIT element of ceruloplasmin mRNA within the translation initiation complexOrthophosphateeIF2:GTPphospho-L13a 60S ribosomal proteineIF4FeIF1AeIF5eIF4BeIF148S complexCeruloplasmin mRNA:eIF4F:eIF4B:eIF4HeIF3 subunits complex80S:Met-tRNAi:mRNA40S:eIF3:eIF1AeIF4E:4E-BPeIF2B subunits complex43S complexeIF4E43S:mRNA:eIF4F:eIF4B:eIF4HMet-tRNAieIF4HeIF2:GDPGTPL13a kinaseOrthophosphateeIF1A40S:Met-tRNAi:mRNAeIF2 subunit complexRNA-binding protein in RNP (ribonucleoprotein) complexeseIF5B:GTPOrthophosphateeIF1AeIF2:GDP: eIF2BADP60s ribosomal complex lacking L13a subunitATPADPternary complexGDP80S:Met-tRNAi:mRNA:eIF5B:GTPOrthophosphateeIF4F:mRNPATPeIF2:GTPeIF2 subunit complex60S ribosomal complexmRNA:eIF4F:eIF4B:eIF4H60S ribosomal protein L13aATP4E-BP1, 21, 21, 21, 2


Description

Initiation of translation in the majority of eukaryotic cellular mRNAs depends on the 5'-cap (m7GpppN) and involves ribosomal scanning of the 5' untranslated region (5'-UTR) for an initiating AUG start codon. Therefore, this mechanism is often called cap-dependent translation initiation. Proximity to the cap, as well as the nucleotides surrounding an AUG codon, influence the efficiency of the start site recognition during the scanning process. However, if the recognition site is poor enough, scanning ribosomal subunits will ignore and skip potential starting AUGs, a phenomenon called leaky scanning. Leaky scanning allows a single mRNA to encode several proteins that differ in their amino-termini. Several eukaryotic cell and viral mRNAs initiate translation by an alternative mechanism that involves internal initiation rather than ribosomal scanning. These mRNAs contain complex nucleotide sequences, called internal ribosomal entry sites, where ribosomes bind in a cap-independent manner and start translation at the closest downstream AUG codon.

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Bibliography

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  1. Pause A, Belsham GJ, Gingras AC, Donzé O, Lin TA, Lawrence JC, Sonenberg N.; ''Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.''; PubMed Europe PMC Scholia
  2. Sampath P, Mazumder B, Seshadri V, Fox PL.; ''Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3' untranslated region.''; PubMed Europe PMC Scholia
  3. Pestova TV, Borukhov SI, Hellen CU.; ''Eukaryotic ribosomes require initiation factors 1 and 1A to locate initiation codons.''; PubMed Europe PMC Scholia
  4. Mazumder B, Sampath P, Seshadri V, Maitra RK, DiCorleto PE, Fox PL.; ''Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control.''; PubMed Europe PMC Scholia
  5. Grifo JA, Tahara SM, Morgan MA, Shatkin AJ, Merrick WC.; ''New initiation factor activity required for globin mRNA translation.''; PubMed Europe PMC Scholia
  6. Safer B, Adams SL, Anderson WF, Merrick WC.; ''Binding of MET-TRNAf and GTP to homogeneous initiation factor MP.''; PubMed Europe PMC Scholia
  7. Pestova TV, Shatsky IN, Hellen CU.; ''Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preinitiation complexes.''; PubMed Europe PMC Scholia
  8. Merrick WC.; ''Eukaryotic protein synthesis: still a mystery.''; PubMed Europe PMC Scholia
  9. Kozak M.; ''Evaluation of the "scanning model" for initiation of protein synthesis in eucaryotes.''; PubMed Europe PMC Scholia
  10. Chakrabarti A, Maitra U.; ''Function of eukaryotic initiation factor 5 in the formation of an 80 S ribosomal polypeptide chain initiation complex.''; PubMed Europe PMC Scholia
  11. Trachsel H, Erni B, Schreier MH, Staehelin T.; ''Initiation of mammalian protein synthesis. II. The assembly of the initiation complex with purified initiation factors.''; PubMed Europe PMC Scholia
  12. Rowlands AG, Panniers R, Henshaw EC.; ''The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2.''; PubMed Europe PMC Scholia
  13. Iost I, Dreyfus M, Linder P.; ''Ded1p, a DEAD-box protein required for translation initiation in Saccharomyces cerevisiae, is an RNA helicase.''; PubMed Europe PMC Scholia
  14. Benne R, Hershey JW.; ''The mechanism of action of protein synthesis initiation factors from rabbit reticulocytes.''; PubMed Europe PMC Scholia
  15. Schreier MH, Erni B, Staehelin T.; ''Initiation of mammalian protein synthesis. I. Purification and characterization of seven initiation factors.''; PubMed Europe PMC Scholia
  16. Sonenberg N, Rupprecht KM, Hecht SM, Shatkin AJ.; ''Eukaryotic mRNA cap binding protein: purification by affinity chromatography on sepharose-coupled m7GDP.''; PubMed Europe PMC Scholia
  17. Dever TE, Wei CL, Benkowski LA, Browning K, Merrick WC, Hershey JW.; ''Determination of the amino acid sequence of rabbit, human, and wheat germ protein synthesis factor eIF-4C by cloning and chemical sequencing.''; PubMed Europe PMC Scholia
  18. Merrick WC, Kemper WM, Anderson WF.; ''Purification and characterization of homogeneous initiation factor M2A from rabbit reticulocytes.''; PubMed Europe PMC Scholia
  19. Asano K, Clayton J, Shalev A, Hinnebusch AG.; ''A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo.''; PubMed Europe PMC Scholia
  20. Peterson DT, Merrick WC, Safer B.; ''Binding and release of radiolabeled eukaryotic initiation factors 2 and 3 during 80 S initiation complex formation.''; PubMed Europe PMC Scholia
  21. Goumans H, Thomas A, Verhoeven A, Voorma HO, Benne R.; ''The role of eIF-4C in protein synthesis initiation complex formation.''; PubMed Europe PMC Scholia
  22. Imataka H, Gradi A, Sonenberg N.; ''A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation.''; PubMed Europe PMC Scholia
  23. Chuang RY, Weaver PL, Liu Z, Chang TH.; ''Requirement of the DEAD-Box protein ded1p for messenger RNA translation.''; PubMed Europe PMC Scholia
  24. Lahn BT, Page DC.; ''Functional coherence of the human Y chromosome.''; PubMed Europe PMC Scholia
  25. Yoder-Hill J, Pause A, Sonenberg N, Merrick WC.; ''The p46 subunit of eukaryotic initiation factor (eIF)-4F exchanges with eIF-4A.''; PubMed Europe PMC Scholia
  26. Pestova TV, Lomakin IB, Lee JH, Choi SK, Dever TE, Hellen CU.; ''The joining of ribosomal subunits in eukaryotes requires eIF5B.''; PubMed Europe PMC Scholia
  27. Damoc E, Fraser CS, Zhou M, Videler H, Mayeur GL, Hershey JW, Doudna JA, Robinson CV, Leary JA.; ''Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry.''; PubMed Europe PMC Scholia
  28. Majumdar R, Bandyopadhyay A, Maitra U.; ''Mammalian translation initiation factor eIF1 functions with eIF1A and eIF3 in the formation of a stable 40 S preinitiation complex.''; PubMed Europe PMC Scholia
  29. Dholakia JN, Wahba AJ.; ''Mechanism of the nucleotide exchange reaction in eukaryotic polypeptide chain initiation. Characterization of the guanine nucleotide exchange factor as a GTP-binding protein.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
128373view17:49, 3 February 2024Ash iyerFixing error (check)
128372view17:45, 3 February 2024Ash iyeridentifier added
128371view17:43, 3 February 2024Ash iyereif1 identifier added.
128323view00:28, 1 February 2024EweitzOntology Term : 'translation pathway' added !
117720view12:33, 22 May 2021EweitzModified title
114979view16:50, 25 January 2021ReactomeTeamReactome version 75
113423view11:49, 2 November 2020ReactomeTeamReactome version 74
112625view16:00, 9 October 2020ReactomeTeamReactome version 73
101541view11:40, 1 November 2018ReactomeTeamreactome version 66
101076view21:23, 31 October 2018ReactomeTeamreactome version 65
100606view19:57, 31 October 2018ReactomeTeamreactome version 64
100157view16:42, 31 October 2018ReactomeTeamreactome version 63
99707view15:11, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99288view12:46, 31 October 2018ReactomeTeamreactome version 62
93969view13:48, 16 August 2017ReactomeTeamreactome version 61
93568view11:27, 9 August 2017ReactomeTeamreactome version 61
86670view09:23, 11 July 2016ReactomeTeamreactome version 56
83337view10:49, 18 November 2015ReactomeTeamVersion54
76969view08:25, 17 July 2014ReactomeTeamFixed remaining interactions
76674view12:04, 16 July 2014ReactomeTeamFixed remaining interactions
76136view13:23, 11 June 2014AnweshaRe-fixing comment source
75707view11:05, 10 June 2014ReactomeTeamReactome 48 Update
75062view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74706view08:46, 30 April 2014ReactomeTeamReactome46
45250view18:36, 7 October 2011AlexanderPicoOntology Term : 'translation initiation pathway' added !
42035view21:51, 4 March 2011MaintBotAutomatic update
39838view05:52, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
40S ribosomal

complex

ComplexREACT_5094 (Reactome)
40S:Met-tRNAi:

mRNA

ComplexREACT_3073 (Reactome)
40S:eIF3:eIF1A ComplexREACT_2456 (Reactome)
43S complex ComplexREACT_3677 (Reactome)
43S: Ceruloplasmin

mRNA:eIF4F:eIF4B: eIF4H:PABP

ComplexREACT_3267 (Reactome)
43S:mRNA:eIF4F:

eIF4B:eIF4H

ComplexREACT_4439 (Reactome)
48S complex ComplexREACT_5152 (Reactome)
4E-BP ProteinQ13541 (UniProt)
60S ribosomal

complex

ComplexREACT_2629 (Reactome)
60S ribosomal

protein L13a

ProteinP40429 (UniProt)
60s ribosomal

complex lacking L13a subunit

ComplexREACT_4690 (Reactome)
80S ribosome ComplexREACT_4330 (Reactome)
80S:Met-tRNAi:

mRNA

ComplexREACT_4537 (Reactome)
80S:Met-tRNAi:

mRNA:eIF5B:GTP

ComplexREACT_2486 (Reactome)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Ceruloplasmin

mRNA:eIF4F:eIF4B: eIF4H

ComplexREACT_2288 (Reactome)
GDP Metabolite17552 (ChEBI)
GTP Metabolite15996 (ChEBI)
L13a

kinase

UnknownREACT_6440 (Reactome)
Met-tRNAi UnknownREACT_4829 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
PABP ProteinP11940 (UniProt)
RNA-binding protein

in RNP (ribonucleoprotein) complexes

UnknownREACT_3670 (Reactome)
eIF1 UnknownREACT_3030 (Reactome)
eIF1A ProteinP47813 (UniProt)
eIF2 subunit

complex

ComplexREACT_5135 (Reactome)
eIF2:GDP ComplexREACT_2996 (Reactome)
eIF2:GDP: eIF2B ComplexREACT_3553 (Reactome)
eIF2:GTP ComplexREACT_3909 (Reactome)
eIF2B subunits

complex

ComplexREACT_3897 (Reactome)
eIF3 subunits

complex

ComplexREACT_4891 (Reactome)
eIF4A subunits

complex

ComplexREACT_5786 (Reactome)
eIF4B ProteinP23588 (UniProt)
eIF4E ProteinP06730 (UniProt)
eIF4E:4E-BP ComplexREACT_3978 (Reactome)
eIF4F ComplexREACT_4441 (Reactome)
eIF4F:mRNP ComplexREACT_4731 (Reactome)
eIF4G ProteinQ04637 (UniProt)
eIF4H ProteinQ15056 (UniProt)
eIF5 ProteinP55010 (UniProt)
eIF5B:GDP ComplexREACT_4697 (Reactome)
eIF5B:GTP ComplexREACT_3457 (Reactome)
mRNA:eIF4F:eIF4B:

eIF4H

ComplexREACT_2596 (Reactome)
mRNP ComplexREACT_3493 (Reactome)
phospho-L13a

60S ribosomal protein

ProteinP40429 (UniProt)
phospho-L13a

associated wth the 3' UTR GAIT element of ceruloplasmin mRNA within the translation initiation complex

ComplexREACT_5151 (Reactome)
ternary complex ComplexREACT_4168 (Reactome)

Annotated Interactions

No annotated interactions

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