Open AccessRACK1 evolved species-specific multifunctionality in translational control through sequence plasticity in a loop domain
Author(s) -
Madeline G. Rollins,
Sujata Jha,
Elizabeth T. Bartom,
Derek Walsh
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.228908
Subject(s) - biology , translation (biology) , eif4e , microbiology and biotechnology , untranslated region , five prime untranslated region , translational regulation , biogenesis , internal ribosome entry site , genetics , rna , messenger rna , gene
Receptor of Activated C Kinase 1 (RACK1) is a highly conserved eukaryotic protein that regulates several aspects of mRNA translation, yet how it does so remains poorly understood. Here we show that although RACK1 consists largely of conserved β-propeller domains that mediate binding to several other proteins, a short interconnecting loop between two of these blades varies across species to control distinct RACK1 functions during translation. Mutants and chimeras revealed that the amino acid composition of the loop is optimized to regulate interactions with eIF6, a eukaryotic initiation factor that controls 60S biogenesis and 80S ribosome assembly. Separately, phylogenetics revealed that despite broad sequence divergence in the loop there is striking conservation of negatively charged residues amongst protists and dicot plants, which is reintroduced to mammalian RACK1 by poxviruses through phosphorylation. While both charged and uncharged loop mutants affect eIF6 interactions, only a negatively charged plant, but not uncharged yeast or human loop enhances translation of mRNAs with adenosine-rich 5’ untranslated regions (UTRs). Our findings reveal how sequence plasticity in the RACK1 loop confers multifunctionality in translational control across species.