Tumor-specific, hypomodified phenylalanyl-tRNA is utilized in translation in preference to the fully modified isoacceptor of normal cells.
Phenylalanine transfer RNA (tRNAPhe) of mammalian tissues contains the hypermodified guanine derivative Y (Wye) adjacent to the 3'-end of the anticodon and two O-methylated bases in the 5' portion of the anticodon loop. These positions are hypomodified in a variety of tumor cells including a mouse neuroblastoma. The normal and tumor-specific Phe-tRNAPhe iso-acceptors were prepared from mouse liver and mouse neuroblastoma cells and compared for their activity in incorporating phenylalanine into each phenylalanine site of rabbit globin in a reticulocyte cell-free protein synthesizing system. The hypomodified Phe-tRNAPhe of neuroblastoma cells is generally preferred to the fully modified tRNAPhe of liver in globin synthesis by about 15%. This preference is the same in the translation of both phenylalanine codons, UUC and UUU, but the ratios of incorporation by the Phe-tRNAPhe species vary from site to site within a 2-fold range. Only 2 of 16 phenylalanine residues are donated preferentially by the fully modified Phe-tRNAPhe. One such residue occurs in beta-42, the second of two tandem phenylalanine residues (both encoded by UUC), while the hypomodified isoacceptor is preferred in translation of the first residue. This result indicates that the translation of tandem residues is particularly affected by the tRNAs available. Since the tumor-specific hypomodified Phe-tRNAPhe is generally utilized preferntially, it appears that the bulky Y base and/or other modifications of normal tRNAPhe may modulate protein synthesis and that tumor cells may achieve a growth advantage if their tRNAPhe is hypomodified.
D000818:Animals; D002460:Cell Line; D005914:Globins / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008815:Mice, Inbred Strains; D009447:Neuroblastoma / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D014176:Protein Biosynthesis; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity
D046911:Macromolecular Substances; D010446:Peptide Fragments; D012346:RNA, Transfer, Amino Acyl; C012099:wye; D006147:Guanine; D005914:Globins