Selective mRNA translation during regeneration

While extensive work has defined transcriptional programs of regeneration, protein abundance frequently diverges from transcript levels, indicating that post-transcriptional regulation may be a critical but underexplored determinant of regenerative capacity. 

Our work identifies Eif4e1c, a homolog of the canonical mRNA cap-binding translation initiation factor eIF4E, as a previously unrecognized regulator of cardiac regeneration. Canonical eIF4E is highly conserved from yeast to humans, whereas Eif4e1c is present across fish evolution but absent from terrestrial vertebrates. Zebrafish lacking eif4e1c show reduced efficiency and magnitude of CM proliferation during the peak regenerative window, despite ultimately completing regeneration. Ribosome profiling further reveals that loss of Eif4e1c selectively alters translation efficiency of transcripts associated with regenerative pathways.

Strikingly, deletion of canonical paralogs instead enhances regeneration, suggesting that regenerative capacity is governed not simply by overall translation activity but by selective translation of specific mRNAs. Moreover, our genetic experiments suggest that it is the balance between cap-binding proteins rather than the presence/absence of either one that tunes regenerative output. This provides a mechanistic framework to dissect selective translation as a quantitative regulatory principle governing regenerative capacity.