Eukaryotic translation initiation factor 3 (eIF3) plays a central role in translation initiation and consists of five core (conserved) subunits present in both budding yeast and higher eukaryotes. Higher eukaryotic eIF3 contains additional (noncore or nonconserved) subunits of poorly defined function, including sub-unit h (eIF3h), which in zebrafish is encoded by two distinct genes (eif3ha and eif3hb). Previously we showed that eif3ha encodes the predominant isoform during zebrafish embryogenesis and that depletion of this factor causes defects in the development of the brain and eyes. To investigate the molecular mechanism governing this regulation, we developed a genome-wide polysome-profiling strategy using stagematched WT and eif3ha morphant zebrafish embryos. This strategy identified a large set of predominantly neural-associated translationally regulated mRNAs. A striking finding was a cohort of lensassociated crystallin isoform mRNAs lost from the eif3ha morphant polysomes, revealing a mechanism by which lens development is translationally controlled. We show that both UTR sequences of a targeted crystallin transcript are necessary but not suf ficient for translational regulation by eif3ha. Therefore, our study reveals the role of a noncore eIF3 subunit in modulating a specific developmental program by regulating translation of defi ned transcripts and highlights the potential of the zebrafish system to identify translational regulatory mechanisms controlling vertebrate development.
|Number of pages
|Proceedings of the National Academy of Sciences of the United States of America
|Published - Jun 11 2013
- RNA sequencing
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