Cell Cycle–Dependent Translation Initiation: IRES Elements Prevail

Once mRNA is transcribed from DNA, its level of expression is dependent upon the efficiency of a number of interconnected cellular processes. These include polyadenylation and splicing in the nucleus, mRNA export, and degradation and localization in the cytoplasm. The expression of an individual mRNA also depends upon the activity of the translational machinery, and the presence or absence of sequence elements that either activate or inhibit its translation. This minireview will describe recent work examining how specific mRNA sequences overcome the general inhibition of translation that occurs in the G2/M phase of the cell cycle. Proper execution of the cell cycle requires that certain proteins be present or active at specific times. Previous work in this well-studied area has described intricate controls involving both transcriptional and posttranslational (modification/proteolysis) regulation that allow for this temporal control. Little work has been done, however, on understanding the role of cell cycle-specific translational control. It has been known that cells arrested in the G2/M phase or in mitosis translate at about 25% the rate of interphase cells, and that this is in part due to an inhibition of the translation initiation step. This inhibition occurs as a result of loss of the cap binding protein's ability to bind to the cap structure, and thus is thought to reflect a general loss of cap-dependent translation in this phase of the cell cycle.