CHOP/GADD153 and methionyl-tRNA synthetase (MetRS) genes overlap in a conserved region that controls mRNA stability.
The transcription factor CHOP is involved in the regulation of the cell division cycle and the control of programmed cell death in response to cellular stress. CHOP expression has been linked with several forms of cancer. A reciprocal translocation between the CHOP and TLS RNA-binding protein gene results in myxoid liposarcoma and amplifications of the CHOP gene are associated with solid tumors including several types of sarcomas. Here we report the mapping of the methionyl tRNA synthetase (MetRS) gene to the identical 12q13 locus where the CHOP gene had previously been mapped. PCR analysis demonstrates a tail-to-tail overlap of both genes over a 55-bp region. As a result the two mRNAs share a 3' UTR complementary sequence allowing an in vivo interaction between the two mRNAs. An AU-rich regulatory element (ARE) known to control mRNA stability resides in the overlapping sequence. To test for functional significance of the ARE a luciferase reporter plasmid containing the 3'UTR of CHOP was constructed. Transfection experiments in NIH-3T3 cells show that CHOP 3'UTR confers a significantly lower activity than a control reporter or a reporter in which the region overlapping the MetRS mRNA is deleted. The conservation of this overlapping of the CHOP and MetRS genes and the role of their complementary sequence in the control of mRNA stability suggest the existence of a functional link between the expression of these two genes.
Ubeda
M
M
Massachusetts General Hospital, Howard Hughes Medical Institute, Boston, Massachusetts 02114, USA.
Schmitt-Ney
M
M
Ferrer
J
J
Habener
J F
JF
D020413:3' Untranslated Regions / Q000235:genetics; D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D005807:Genes, Overlapping / Q000235:genetics*; D006801:Humans; D008718:Methionine-tRNA Ligase / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D020413:3' Untranslated Regions; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D008718:Methionine-tRNA Ligase