Colón-Ramos Daniel A, Shenvi Christina L, Weitzel Douglas H, Gan Eugene C, Matts Robert, Cate Jamie, Kornbluth Sally
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nat Struct Mol Biol. 2006 Feb;13(2):103-11. doi: 10.1038/nsmb1052. Epub 2006 Jan 22.
During apoptosis and under conditions of cellular stress, several signaling pathways promote inhibition of cap-dependent translation while allowing continued translation of specific messenger RNAs encoding regulatory and stress-response proteins. We report here that the apoptotic regulator Reaper inhibits protein synthesis by binding directly to the 40S ribosomal subunit. This interaction does not affect either ribosomal association of initiation factors or formation of 43S or 48S complexes. Rather, it interferes with late initiation events upstream of 60S subunit joining, apparently modulating start-codon recognition during scanning. CrPV IRES-driven translation, involving direct ribosomal recruitment to the start site, is relatively insensitive to Reaper. Thus, Reaper is the first known cellular ribosomal binding factor with the potential to allow selective translation of mRNAs initiating at alternative start codons or from certain IRES elements. This function of Reaper may modulate gene expression programs to affect cell fate.
在细胞凋亡过程以及细胞应激条件下，多种信号通路会促进对帽依赖性翻译的抑制，同时允许编码调节蛋白和应激反应蛋白的特定信使核糖核酸（mRNA）持续翻译。我们在此报告，凋亡调节因子收割者（Reaper）通过直接结合40S核糖体亚基来抑制蛋白质合成。这种相互作用既不影响起始因子与核糖体的结合，也不影响43S或48S复合物的形成。相反，它会干扰60S亚基加入上游的后期起始事件，明显在扫描过程中调节起始密码子的识别。克氏锥虫内部核糖体进入位点（CrPV IRES）驱动的翻译，涉及核糖体直接募集到起始位点，对收割者相对不敏感。因此，收割者是首个已知的细胞核糖体结合因子，有潜力允许在替代起始密码子处起始或从某些IRES元件起始的mRNA进行选择性翻译。收割者的这一功能可能会调节基因表达程序以影响细胞命运。
