Fig. 5

Translational rewiring uncovered by ribosome profiling in cancers. This figure summarizes some of the changes in the translation process in cancer cells, as revealed through ribosome profiling. In addition, ribosome profiling has shown the ability to aid in the discovery of noncanonical ORFs, such as lncRNA ORFs, microRNA ORFs, and circORFs. In addition to its canonical role in stabilizing p53 protein, ARF impairs the translation of mRNA containing 5’ -TOP motif, many of which encode translation factors and many ribosomal proteins, via downregulating the expression of eIF4G1 and LARP1. FTO, an m6A demethylase, enhances the translational efficiency of MYC mRNA in cervical cancer. The lncRNA ASH1L-AS1 encodes a microprotein, APPLE, which is upregulated in various AML subtypes, causing poor prognosis by promoting the PABPC1-eIF4G interaction to support selective oncoprotein synthesis. CDK1 can phosphorylate LARP1 to boost the translation of 5′-TOP mRNAs, stimulating ribosome biogenesis and global translation. EIF2B5 upregulates FBXO32 to selectively inhibit epidermal renewal without affecting the overall proliferation. NSUN6, an m5C RNA methylase, targets consensus sequence motif CTCCA on the 3’UTR of RNA transcripts thus elevating their translational efficiencies. Red arrows and blue “T” shapes stand for promotive and inhibitory effects respectively. Characters in blue represents micropeptides/microproteins encoded by lncRNAs