Molecular Cell
Molecular Cell
4 years ago

Structural and Functional Insights into Human Re-initiation Complexes

Structural and Functional Insights into Human Re-initiation Complexes
After having translated short upstream open reading frames, ribosomes can re-initiate translation on the same mRNA. This process, referred to as re-initiation, controls the translation of a large fraction of mammalian cellular mRNAs, many of which are important in cancer. Key ribosomal binding proteins involved in re-initiation are the eukaryotic translation initiation factor 2D (eIF2D) or the homologous complex of MCT-1/DENR. We determined the structures of these factors bound to the human 40S ribosomal subunit in complex with initiator tRNA positioned on an mRNA start codon in the P-site using a combination of cryoelectron microscopy and X-ray crystallography. The structures, supported by biochemical experiments, reveal how eIF2D emulates the function of several canonical translation initiation factors by using three independent, flexibly connected RNA binding domains to simultaneously monitor codon-anticodon interactions in the ribosomal P-site and position the initiator tRNA.

Graphical abstract

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Teaser

Weisser et al. solve the structures of re-initiation factors in complex with the small ribosomal subunit, mRNA, and initiator tRNA. The structures reveal how re-initiation factors monitor start codon recognition and position the initiator tRNA to mimic the functions of canonical translation initiation factors.

Publisher URL: www.sciencedirect.com/science

DOI: S1097276517304902

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