Transcript Termination in Translation

Termination of Translation
Chris Avins
Elizabeth Durante
Christine Noonan
Basic Mechanism
• 1. Elongation stops when a stop codon reaches
A site of ribosome
Basic Mechanism
• 2. Release factor binds to stop codon
Basic Mechanism
• 3. Release factor adds H2O instead of an amino
acid
• 4. Bond is broken and polypeptide chain is freed
tRNA
Release Factors
• Basic function: release
polypeptide chain from
mRNA
• There are two release
factors that work together in
order to terminate
translation (eRF1 & eRF3
in eukaryotes) (RF1/RF2 &
RF3 in prokaryotes)
Eukaryotic Release Factors
• A stop codon is recognized by the heterodimer
complex of eRF1 and eRF3
• These release factors mimic tRNA structurally and
functionally
– eRF3 triggers GTP hydrolysis, enhancing the rate of
peptidyl release
– It also recycles post-termination ribosomes to 5’ end to
begin initiation again
The Termination Signal
• eRF1 recognizes all three stop codons
• RF stop codon recognition is up to 60 times
slower than sense codon decoding
• eRF1 accurately discriminates between U-purinepurine codons and other sense codons, interacting
with U-purine-purine codons stabilize eRF1 in a
conformation to proceed to the next step
The Termination Signal
• Codons surrounding the stop codons are not
random. The tetranucleotide is important in
determining the efficiency of termination
• As many as three succeeding nucleotides may
contact the RF and play a role in termination
• 5’ nucleotide context also influences efficiency
Stop Codon Recognition
• 8 protein residues found in eRF1 act in the
physical interaction of eRF1 and mRNA stop
codon that mediate stop codon recognition
• 5 of the proteins were consistent in all analyzed
species
• 3 of the proteins were only the same in species
using the same set of stop codons
• 2 more proteins need more research
• Stop codon selection in eukaryotes is not yet
understood
Prokaryotic Differences
• The job done by eRF1 is divided between RF1
and RF2. Both discriminate between A&G at the
2nd and 3rd positions of stop codons using the PAT
& SPF tripeptides
• Peptidyl release is independent of RF3
• RF3 stimulates the termination rxn. and binds
guanine nucleotides but is not codon-specific
• There is no structural resemblance between RF1/2
and RF3 and eRF1 and eRF3 due to evolutionary
origin of translation termination
References
• http://www.ncbi.nlm.nih.gov/pmc/articles/PM
C394485/pdf/emboj00040-0223.pdf
• http://mic.sgmjournals.org/cgi/reprint/147/2/25
5
• http://www.nature.com/emboj/journal/v22/n7/f
ull/7595057a.html
• http://www.springerlink.com/content/lx223777
867w3521/fulltext.pdf