translation initiation
- Created by: natasha8sherry
- Created on: 11-01-14 12:29
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- Translation initiation
- Aim is to recruit the small ribosomal subunit and an initiator tRNA charged with methionine to the mRNA molecule
- AUG start codon needs to be found on the mRNA
- process guided by translation initiation factors
- IFs in prokaryotes and eIFs in eukaryotes
- small 40S ribosomal subunit recruited via the 7-methylguanosine cap at the 5' end of mRNA
- relies on a complex of initiation factors called eIF4F
- eIF4E
- eIF4A
- eIF4G
- eIF4E protein binds the 5' cap and locks the eIF4F complex onto the mRNA
- 40S subunit recruited with the initiator tRNA
- aided by
- eIF2
- eIF5B
- this forms the 43S pre-initiation complex
- 40S subunit and associated factors scan the 5'UTR to find the first start codon
- eIF4A aids this
- RNA helicase that unwinds stem loop structures in the 5'UTR that otherwise impede translation initiation
- eIF4B required to activate eIF4A
- PolyA tail stimulates translation by sending ribosomes which have just ended a round of transcription back to the 3' end for another
- uses the eIF4G subunit of eIF4F
- interacts with the polyA binding protein PAB2, causing the mRNA to form a closed loop structure, resulting in the closed-loop model of transcription
- uses the eIF4G subunit of eIF4F
- eIF4A aids this
- 40S subunit and associated factors scan the 5'UTR to find the first start codon
- aided by
- 40S subunit recruited with the initiator tRNA
- relies on a complex of initiation factors called eIF4F
- occurs in the cytoplasm as intracellular mechanisms prevent mRNAs from interacting with ribosomal subunits inside the nulceus
- this prevents 80S formation
- non-ribosomal association factors (NAFs) also prevent 80S formation in nucleus
- pre-40S rRNA is not fully processed as it has a pre-20S rRNA component which needs to be cleaved to an 18S component
- However, recent studies showed that many ribosomal proteins, rRNAs and TFs associate with nascent transcripts in the nucleus
- study has also found that radioactive AAs are incorporated at chromosomes of polytenic nuclei.
- a recent study by al-jubran also found that 80s ribosomes are present in the nucleus
- Non-AUG start codons
- translation can be initiated from a non-AUG start codon in proks and euks
- in euks these start from CUG and UUG
- e.g. the FGF-2 growth factor gene can start translation from typical AUG but also from 3 separate CUG codons where the initiator tRNA is charged with leucine
- these resultant isoforms of the FGF-2 protein have differing physiological properties and induce expression of different genes
- examples of a group of alternative translation start sites called INTERNAL RIBOSOME ENTRY SITES
- also present in prok polycistronic mRNAs so that the ribosome can bypass the most upstream AUG and instead initiate transcription at a downstream AUG start codon
- not confined to viruses
- in euks associated with stress and mitosis
- in mitosis, cells dephosphorylate eIF4E, reducing its affinity for the 5'-cap
- causes the translation machinery to preferentially translate from IRES sequences
- IRES-containing mRNAs allow for translation also when regular translational pathways become unavailable due to viral infection
- some viruses operate by shutting down the host cell translation by destroying the euk initiation factor eIF4G, preventing the interaction between the 5'cap and polyA tail - closed-loop structure cannot form
- the viral mRNAs then take over the translation machinery using their IRES sequences
- some viruses operate by shutting down the host cell translation by destroying the euk initiation factor eIF4G, preventing the interaction between the 5'cap and polyA tail - closed-loop structure cannot form
- in mitosis, cells dephosphorylate eIF4E, reducing its affinity for the 5'-cap
- in euks associated with stress and mitosis
- e.g. the FGF-2 growth factor gene can start translation from typical AUG but also from 3 separate CUG codons where the initiator tRNA is charged with leucine
- very rare
- in euks these start from CUG and UUG
- translation can be initiated from a non-AUG start codon in proks and euks
- Aim is to recruit the small ribosomal subunit and an initiator tRNA charged with methionine to the mRNA molecule
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