Ph.D Candidate ( Graduate Student ) Pohang University of Science and Technology (POSTECH) Nam-gu, Pohang-si, Kyongsang-bukto, Republic of Korea
Abstract: The integrated stress response (ISR) suppresses global translation while allowing the selective translation of key regulatory genes. However, how protein synthesis persists during ISR remains unclear. In eukaryotic cells, the 5′-cap of most mRNAs is bound by either the nuclear cap-binding complex (CBC) or the cytosolic cap-binding protein eIF4E. Our study reveals that under stress conditions, CBC-bound mRNAs utilize eIF2A, an alternative translation initiation factor, to maintain protein synthesis when translation of eIF4E-bound mRNAs is inhibited. Human embryonic stem cells (hESCs), which inherently exhibit ISR, actively proliferate because of a compensatory increase in the eIF2A expression. This increase ensures CBC-dependent translation (CT) and supports the synthesis of essential cell cycle proteins during stress. Notably, YAP, a key proliferation factor, is a critical CT target driving stress-resistant stem cell proliferation. Therefore, our findings highlight CT as a crucial pathway that protects protein synthesis and supports stem cell proliferation during stress.
Funding Source: National Research Foundation (NRF) of Korea grant funded by the Korean government
