Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein, NM23-LV.
NM23-H1 and NM23-H2 are neighboring genes on chromosome 17q. They encode nucleoside diphosphate kinases that have additional roles in signal transduction, transcription, and apoptosis. NM23-H1 expression is a strong marker for prognosis and metastatic behavior in many tumor types. A new bioinformatic tool, TranscriptView, identified read-through transcripts that start in the NM23-H1 gene and continue in the neighboring NM23-H2 gene. Splicing results in a transcript containing exons 1 to 4 of NM23-H1 and exons 2 to 5 of NM23-H2. The resulting mRNA encodes a novel and long variant of the NM23 protein family, NM23-LV, which contains part of NM23-H1 and the complete NM23-H2 protein. The transcript was amplified and sequenced from two neuroblastoma cell lines, confirming the presence of the predicted NM23-LV mRNA in vivo. Tissue analysis showed that NM23-LV is ubiquitously expressed, with the exception of the kidney. Neuroblastoma tumors show high-level expression of NM23-H1 and-H2 as well as NM23-LV mRNA. In neuroblastoma cells, the NM23-LV protein has mainly a cytoplasmic localization, but some nuclear staining was observed as well.
Valentijn
Linda J
LJ
Department of Human Genetics, M1-134, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. L.J.Valentijn@amc.uva.nl
Koster
Jan
J
Versteeg
Rogier
R
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17; D019295:Computational Biology; D003593:Cytoplasm / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D020224:Expressed Sequence Tags; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D054778:NM23 Nucleoside Diphosphate Kinases; D009447:Neuroblastoma / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012235:Rhodamines; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D012235:Rhodamines; C009434:tetramethylrhodamine isothiocyanate; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase