Regulation of Translation Initiation Protein level

protein-level control involve

modifications of eIF2

Post-translational modifications can

change protein properties, structure, function

Post-translational modifications ex 1

Modifications to histone tails change the nucleosome interaction with DNA, other proteins in chromatin

Post-translational modifications ex 2

Phosphorylation of specific parts of the RNA Pol II C-terminal domain controls which proteins can bind and modify mRNAs

The activity of Initiation Factor 2 is

controlled by phosphorylation

eIF2 phosphorylation

inactivates it

eIF2 phosphorylation 1

during translation initiation eIF2 unbinds GDP

binds GTP facilitated by binding to a protein called a GEF

eIF2 phosphorylation 2

phosphorylation by Gcn2 locks eIF2 in the GDP-bound, GEF-bound state

eIF2 phosphorylation 3

Gcn2 binds unchanged tRNAs

eIF2 phosphorylation 4

low [amino acid] reduces the amount of aa-tRNA compared to uncharged tRNAs

Phosphorylation of eIF2 affects

all translation

eIF2 is important for

global translation initiation

this is not transcript-specific

• Under starvation conditions,

preventing initiation is preferred over allowing ribosomes to stall, which would cause mRNAs to be degraded by non-sense-mediated decay