Upregulation of eIF5B controls cell-cycle arrest and specific developmental stages.

Abstract

Proliferation arrest and distinct developmental stages alter and decrease general translation yet maintain ongoing translation. The factors that support translation in these conditions remain to be characterized. We investigated an altered translation factor in three cell states considered to have reduced general translation: immature Xenopus laevis oocytes, mouse ES cells, and the transition state of proliferating mammalian cells to quiescence (G0) upon growth-factor deprivation. Our data reveal a transient increase of eukaryotic translation initiation factor 5B (eIF5B), the eukaryotic ortholog of bacterial initiation factor IF2, in these conditions. eIF5B promotes 60S ribosome subunit joining and pre-40S subunit proofreading. eIF5B has also been shown to promote the translation of viral and stress-related mRNAs and can contribute indirectly to supporting or stabilizing initiator methionyl tRNA (tRNA-Met(i)) association with the ribosome. We find that eIF5B is a limiting factor for translation in these three conditions. The increased eIF5B levels lead to increased eIF5B complexes with tRNA-Met(i) upon serum starvation of THP1 mammalian cells. In addition, increased phosphorylation of eukaryotic initiation factor 2α, the translation factor that recruits initiator tRNA-Meti for general translation, is observed in these conditions. Importantly, we find that eIF5B is an antagonist of G0 and G0-like states, as eIF5B depletion reduces maturation of G0-like, immature oocytes and hastens early G0 arrest in serum-starved THP1 cells. Consistently, eIF5B overexpression promotes maturation of G0-like immature oocytes and causes cell death, an alternative to G0, in serum-starved THP1 cells. These data reveal a critical role for a translation factor that regulates specific cell-cycle transition and developmental stages.

• Authors: Sooncheol Lee, Samuel S Truesdell, Syed I A Bukhari, Ju Huck Lee, Olivier LeTonqueze, Shobha Vasudevan
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 41 Pg. E4315-22 (Oct 14 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 25261552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Serum-Free
• Eukaryotic Initiation Factor-2
• Eukaryotic Initiation Factors
• RNA, Transfer, Met
• eukaryotic initiation factor-5B

Topics

• Animals
• Cell Cycle Checkpoints
• Cell Line
• Cell Survival
• Culture Media, Serum-Free
• Embryonic Stem Cells (cytology, metabolism)
• Eukaryotic Initiation Factor-2 (metabolism)
• Eukaryotic Initiation Factors (genetics, metabolism)
• Humans
• Mice
• Oocytes (cytology, metabolism)
• Phosphorylation
• Protein Biosynthesis
• RNA, Transfer, Met
• Up-Regulation
• Xenopus laevis