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eIF3 engages with 3'-UTR termini of highly translated mRNAs
Santi Mestre-Fos1,2, Lucas Ferguson2,3, Marena I Trinidad1,4
1Innovative Genomics Institute, University of California, Berkeley, Berkeley, United States.
Elife
|January 29, 2025
Summary
Eukaryotic initiation factor 3 (eIF3) binds to the 3' untranslated regions of highly translated mRNAs during stem cell differentiation. This suggests a general role for eIF3 in regulating protein synthesis through mRNA circularization.
Area of Science:
- Molecular Biology
- Stem Cell Biology
- Biochemistry
Background:
- Stem cell differentiation requires increased protein synthesis.
- The mechanisms controlling this translational increase, particularly the role of initiation factors, are not well understood.
Purpose of the Study:
- To investigate the function of eukaryotic initiation factor 3 (eIF3) in human pluripotent stem cell (hPSC)-derived neural progenitor cell (NPC) differentiation.
- To elucidate the molecular mechanisms by which eIF3 influences translation during early differentiation.
Main Methods:
- Utilized Quick-irCLIP and alternative polyadenylation (APA) sequencing to map eIF3 binding sites on mRNA.
- Employed ribosome profiling to assess translational activity and efficiency.
- Analyzed the relationship between eIF3 crosslinking, polyadenylation status, and translation.
Main Results:
- eIF3 predominantly crosslinks with the 3' untranslated regions (3'-UTRs) of mRNA isoforms near the poly(A) tail.
- eIF3 binding to 3'-UTR termini is dependent on mRNA polyadenylation.
- High eIF3 crosslinking correlates with high mRNA translational activity, but not necessarily translational efficiency.
Conclusions:
- eIF3 engages with 3'-UTR termini of actively translated mRNAs, indicating a potentially general regulatory role.
- These findings support the involvement of mRNA circularization mechanisms in regulating protein synthesis during stem cell differentiation.
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