Abstract
Initiation factor eIF4G is a key regulator of eukaryotic protein synthesis, recognizing proteins bound at both ends of an mRNA to help recruit messages to the small (40S) ribosomal subunit. Notably, the genomes of a wide variety of eukaryotes encode multiple distinct variants of eIF4G. We found that deletion of eIF4G1, but not eIF4G2, impairs growth and global translation initiation rates in budding yeast under standard laboratory conditions. Not all mRNAs are equally sensitive to loss of eIF4G1; genes that encode messages with longer poly(A) tails are preferentially affected. However, eIF4G1-deletion strains contain significantly lower levels of total eIF4G, relative to eIF4G2-delete or wild type strains. Homogenic strains, which encode two copies of either eIF4G1 or eIF4G2 under native promoter control, express a single isoform at levels similar to the total amount of eIF4G in a wild type cell and have a similar capacity to support normal translation initiation rates. Polysome microarray analysis of these strains and the wild type parent showed that translationally active mRNAs are similar. These results suggest that total eIF4G levels, but not isoform-specific functions, determine mRNA-specific translational efficiency.
Highlights
Translation initiation is the rate-limiting step of protein synthesis in which the ribosomal subunits assemble with initiation factors and an mRNA to form an activated complex
Deletion of TIF4631 Causes a Translation Initiation Defect Prior analysis of Eukaryotic initiation factor 4G (eIF4G) variants in yeast revealed that deletion of TIF4631 impedes cell growth, whereas tif4632D cells grow at wild type rates under standard laboratory conditions [28,37]
To investigate whether this decreased growth rate relates to a protein synthesis defect, we examined the translational profile of wild type (YBC87), tif4631D (YBC88) and tif4632D (YBC89) cells
Summary
Translation initiation is the rate-limiting step of protein synthesis in which the ribosomal subunits assemble with initiation factors and an mRNA to form an activated complex (reviewed in [1]). Capdependent initiation, an mRNA is selected for translation via interactions of its 59 methyl-7-guanosine (m7G) cap and 39 poly(A) tail with the cap binding protein, eIF4E, and poly(A) binding protein, PABP, respectively (reviewed in [1]). EIF4G contributes to message selection by enhancing the affinity of these two factors for their substrates [2,3,4]. EIF4G recruits 40S subunits to mRNAs via simultaneous binding of eIF4E, PABP and factors connected to the 40S [12,13,14]. In addition to its role in canonical translation initiation, eIF4G is required for 59 capindependent translation of some host and viral mRNAs [15,16,17]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call