Mechanisms of Gene Regulation
Kim, Byung-Hoon , Roy, Bijoyita , Cai, Xue , Vaughn, Justin , Zhou, Fujun , Kim, Tae-Houn , von Arnim, Albrecht .
The H subunit of eukaryotic translation initiation factor 3 contributes to the efficient translation of mRNAs with upstream open reading frames.
Upstream open reading frames (uORFs) in 5’ leader sequences often inhibit translation initiation and can play critical roles in signal-dependent regulation of translation. Although over 30% of mRNAs harbor at least one uAUG in Arabidopsis, factors required to overcome or to regulate them are elusive. Here, we demonstrate that the H subunit of eukaryotic translation initiation factor 3 (eIF3) contributes to the efficient translation of mRNAs with uORFs. The H subunit is considered one of the seven non-core subunits with potential regulatory roles in the multifunctional eIF3 complex. The eif3h mutant exhibits a pleiotropic phenotype including hypersensitive sugar response (Plant Cell, 16: 3341). Transient and stable transgene expression of luciferase reporter constructs fused to different 5’ leader sequences indicated that translation of certain genes, such as the sugar-regulated mRNA AtbZip11, was compromised in the eif3h mutant background. Microarray comparisons of polysome loading in wild-type and eif3h mutant seedlings revealed that eIF3h generally helps to maintain efficient polysome loading of mRNA species harboring multiple uORFs independent of transcript level. Functional classification by MapMan further showed that important regulatory gene classes that are enriched in uAUGs, such as transcriptional regulators and protein modifying enzymes, were translationally compromised in the eif3h mutant while other functional subgroups including ribosomal proteins maintained their polysome loading state. In addition, eIF3h boosted the polysome loading of mRNAs with long coding sequences. Taken together, eIF3h functions in translation initiation by overcoming the repressive effect of uORFs, which is particularly pronounced on mRNAs with a long main ORF.
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1 - University of Tennessee, Biochemistry, Cell and Molecular Biology, M407 Walters Life Sciences, Knoxville, TN, 37996, USA
2 - The University of Tennessee, Biochemistry, Cell and Molecular Biology
3 - The Univesity of Tennessee, Graduate School of Genome Science and Technology, Knoxville, Tennessee, 37996, USA
Presentation Type: ASPB Minisymposium
Location: Waldorf Room/Hilton
Date: Monday, July 9th, 2007
Time: 11:30 AM