Fig. 5

Distinct codon usage signature in pluripotent cells are hetADAT-sensitive codons. a Illustration of hetADAT (ADAT2 and ADAT3)-mediated adenosine-to-inosine tRNA editing at position 34 in the anticodon loop and the codons read by unmodified and modified tRNAs. b HetADAT-dependent codons (red) that sometimes are lacking corresponding tRNA genes (light gray). c–f Volcano plot (c, e) showing significance versus codon usage fold change at the ribosome P-site (c) and A-site (e) in differentiated versus self-renewing hESCs. HetADAT-dependent codons are highlighted in red. Correlation (d, f) between log₂ fold change of codon usage frequencies in differentiated human (hESCs) with differentiated mouse (mESCs) embryonic stem cells through embryoid body culture (EB; left-hand panel) or by removal of LIF (right-hand panel) at the P-site (d) and A-site (f). g Log₂ fold change of codon usage frequency across all sites protected by the ribosome in human (left-hand panel) and mouse ESCs differentiated through EB culture (middle panel) or removal of LIF (right-hand panel). HetADAT-dependent codons are highlighted in red