eIF3 targets cell-proliferation messenger RNAs for translational activation or repression

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Protein synthesis regulation is vital for eukaryotic cellular processes, including development and stress responses.
• The 13-subunit eukaryotic initiation factor 3 (eIF3) complex is essential for initiating protein translation.
• Deregulation of eIF3 is linked to cancers and developmental abnormalities, but its specific mRNA targets and regulatory mechanisms remain unclear.

Purpose of the Study:

• To identify human transcripts interacting with eIF3 genome-wide.
• To elucidate the mechanisms by which eIF3 regulates specific mRNA translation.
• To explore the implications of eIF3-mRNA interactions in cellular processes and carcinogenesis.

Main Methods:

• Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to map eIF3-RNA interactions.
• Functional analysis of eIF3 binding to specific mRNAs (c-JUN, BTG1).
• Investigation of RNA stem-loop binding modes for translational control.

Main Results:

• Genome-wide identification of specific mRNAs bound by eIF3, primarily in their 5' untranslated regions.
• eIF3 targets mRNAs involved in cell growth control, including cell cycling, differentiation, and apoptosis.
• eIF3 utilizes distinct RNA stem-loop binding modes to differentially regulate translation of c-JUN and BTG1, acting as both an activator and repressor.

Conclusions:

• eIF3 governs a specialized repertoire of gene expression through direct mRNA binding.
• The dual role of eIF3 in translational activation and repression highlights its complex regulatory function.
• Targeting eIF3-mRNA interactions presents a potential strategy for controlling carcinogenesis.