In eukaryotic translation, a 5' cap-independent mechanism operates via internal ribosome entry sites (IRES) to allow translation of certain mRNAs under stress. Which of the following cellular conditions specifically upregulates IRES-mediated translation while global cap-dependent translation is suppressed?
- A Increased phosphorylation of eIF4E by Mnk1 kinase downstream of MAPK signaling
- B Activation of mTORC1 and phosphorylation of 4E-BP1 releasing eIF4E
- C Phosphorylation of eIF2alpha by stress kinases (HRI, GCN2, PKR, PERK) during the integrated stress response ✓
- D Upregulation of eIF4G expression during G1 phase of the cell cycle
Explanation
During cellular stress (amino acid deprivation, ER stress, viral infection, heme deficiency), eIF2alpha is phosphorylated by stress-sensing kinases (GCN2, PERK, HRI, PKR). This reduces ternary complex availability and globally suppresses cap-dependent translation initiation. Paradoxically, select mRNAs with IRES elements or upstream open reading frames (uORFs) such as ATF4 and CHOP are preferentially translated under these conditions, facilitating the integrated stress response (ISR). mTORC1 activation and 4E-BP1 phosphorylation promote, not suppress, cap-dependent translation.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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