20. Phosphorylation of the a-subunit of elF2 at Ser 51 position in Saccharomyces cerevisiae leads to sequestration of elF2B, guanosine exchange factor. This phenomenon is
(1) known to activate translation of the capped mRNAs in the cytosol
(2) known to activate translation of many key mRNAs possessing short ORFs(uORFs) in the mRNA sequence that proceed the main ORF
(3) an essential requirement for translation of IRES containing mRNAs.
(4) an essential requirement for the transport of mature mRNAs out of the nucleus

Introduction

Phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) at serine 51 is a critical regulatory event in the cellular stress response. In Saccharomyces cerevisiae, this modification inhibits global protein synthesis but paradoxically activates translation of specific mRNAs containing upstream open reading frames (uORFs). This mechanism ensures selective expression of stress-responsive genes, such as GCN4, during nutrient deprivation and other stresses.

Mechanism of uORF-Mediated Translational Control

Under normal conditions, ribosomes initiate translation at uORFs in the 5′ untranslated region (UTR), preventing translation of the downstream main ORF. Phosphorylation of eIF2α reduces the availability of the ternary complex (eIF2-GTP-Met-tRNAi), causing ribosomes to bypass uORFs and initiate translation at the main ORF.

This selective translation allows cells to produce proteins essential for adaptation to stress despite overall translational repression.

Biological Significance

This regulatory mechanism is vital for:

• Stress adaptation: Enabling synthesis of transcription factors and other proteins required under stress.

• Resource conservation: Reducing unnecessary protein synthesis while allowing critical gene expression.

• Gene-specific control: Fine-tuning protein production at the translational level.

Conclusion

Phosphorylation of eIF2α at Ser 51 in yeast is a key event that inhibits general translation but activates selective translation of mRNAs containing uORFs. This mechanism exemplifies the complexity of translational regulation in response to cellular stress.

Answer:
(2) known to activate translation of many key mRNAs possessing short ORFs (uORFs) in the mRNA sequence that precede the main ORF

This explanation highlights the dual role of eIF2α phosphorylation in translational control, emphasizing its importance in yeast stress responses.