eIF3 interacts with histone H4 messenger RNA to regulate its translation

Area of Science:

• Molecular Biology
• Gene Expression Regulation
• Protein Synthesis

Background:

• Histone synthesis is crucial for DNA replication during the S phase.
• Histone mRNA translation utilizes non-canonical mechanisms, including internal initiation.
• The human eukaryotic translation initiation factor 3 (eIF3) complex regulates various cellular mRNAs.

Purpose of the Study:

• To investigate the role of eIF3 in histone mRNA translation.
• To determine if eIF3 binds to histone mRNAs and identify specific subunits involved.
• To elucidate the regulatory function of eIF3 in histone neosynthesis.

Main Methods:

• In vivo and in vitro cross-linking and ribonucleoprotein immunoprecipitation (RIP).
• Identification of eIF3 binding sites on histone mRNAs.
• Analysis of histone synthesis following eIF3 depletion.

Main Results:

• eIF3 directly binds to a stem-loop structure in H4 mRNA (eIF3-BS).
• eIF3 interacts with H1, H2A, H2B, and H3 histone mRNAs via specific subunits (eIF3c, d, e, g).
• Depletion of eIF3 in vivo reduces histone mRNA binding and histone neosynthesis.

Conclusions:

• eIF3 plays a significant role in regulating the translation of histone mRNAs.
• eIF3 acts as a key regulator of histone synthesis, impacting cell cycle progression.
• The findings uncover a novel mechanism controlling the expression of essential cell cycle proteins.