Eukaryotic translation initiation machinery can operate in a bacterial-like mode without eIF2.
Unlike bacteria, a specialized eukaryotic initiation factor (eIF)-2, in the form of the ternary complex eIF2-GTP-Met-tRNA(i) (Met), is used to deliver the initiator tRNA to the ribosome in all eukaryotic cells. Here we show that the hepatitis C virus (HCV) internal ribosome entry site (IRES) can direct translation without eIF2 and its GTPase-activating protein eIF5. In addition to the general eIF2- and eIF5-dependent pathway of 80S complex assembly, the HCV IRES makes use of a bacterial-like pathway requiring as initiation factors only eIF5B (an analog of bacterial IF2) and eIF3. The switch from the conventional eukaryotic mode of translation initiation to the eIF2-independent mechanism occurs when eIF2 is inactivated by phosphorylation under stress conditions.
Terenin
Ilya M
IM
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia.
Dmitriev
Sergey E
SE
Andreev
Dmitry E
DE
Shatsky
Ivan N
IN
D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D004926:Escherichia coli / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D005914:Globins / Q000378:metabolism; D016174:Hepacivirus / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; C451459:eukaryotic initiation factor-5B; D005914:Globins; D012343:RNA, Transfer