The structure of the 5'-end of the protein-tyrosine phosphatase PTPRJ mRNA reveals a novel mechanism for translation attenuation.
Analysis of the human protein-tyrosine phosphatase (PTP) PTPRJ mRNA detected three in-frame AUGs at the 5'-end (starting at nt +14, +191 and +356) with no intervening stop codons. This tandem AUG arrangement is conserved between humans and the mouse and is unique among the genes of the classical PTPs. Until now it was assumed that the principal open reading frame (ORF) starts at AUG(356). Our experiments showed that: (i) translation of the mRNA synthesized under the PTPRJ promoter starts predominantly at AUG(191), leading to the generation of a 55 amino acid sequence preceding the signal peptide; (ii) the longer form is being likewise correctly processed into mature PTPRJ; (iii) the translation of the region between AUG(191) and AUG(356) inhibits the overall expression, a feature which depends on the sequence of the encoded peptide. Specifically, a sequence of 13 amino acids containing multiple arginine residues (RRTGWRRRRRRRR) confers the inhibition. In the absence of uORF these previously unrecognized characteristics of the 5'-end of the mRNA present a novel mechanism to suppress, and potentially to regulate translation.
Karagyozov
Luchezar
L
Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich-Schiller-University Jena, Jena, Germany.
Godfrey
Rinesh
R
Böhmer
Sylvia-Annette
SA
Petermann
Astrid
A
Hölters
Sebastian
S
Ostman
Arne
A
Böhmer
Frank-D
FD
D020121:5' Untranslated Regions / Q000737:chemistry*; D001483:Base Sequence; D002460:Cell Line; D003062:Codon; D018387:Codon, Initiator; D017124:Conserved Sequence; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D010441:Peptide Chain Elongation, Translational; D010442:Peptide Chain Initiation, Translational; D010443:Peptide Chain Termination, Translational; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000096:biosynthesis / Q000235:genetics
D020121:5' Untranslated Regions; D003062:Codon; D018387:Codon, Initiator; D012333:RNA, Messenger; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3