An Intergenic Non-Coding rRNA Correlated with Expression of the rRNA and Frequency of an rRNA Single Nucleotide Polymorphism in Lung Cancer Cells

• Published in: PloS one Vol. 4; no. 10; p. e7505
• Main Authors: Shiao, Yih-Horng, Lupascu, Sorin T., Gu, Yuhan D., Kasprzak, Wojciech, Hwang, Christopher J., Fields, Janet R., Leighty, Robert M., Quiñones, Octavio, Shapiro, Bruce A., Alvord, W. Gregory, Anderson, Lucy M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.10.2009; Public Library of Science (PLoS)
• Subjects: Acids; Analysis; Animals; Bioinformatics; Biotechnology; Cancer; Cancer cells; Cell Line; Cell Line, Tumor; Chromosomes; Cloning; Cloning, Molecular; Correlation; Data analysis; Epithelial cells; Fibroblasts; Fibroblasts - metabolism; Gene expression; Genes; Genetic algorithms; Genetic aspects; Genetics and Genomics/Cancer Genetics; Genetics and Genomics/Epigenetics; Genomics; Hepatitis; Hepatitis delta virus; Humans; Laboratories; Lung - metabolism; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Mice; Models, Genetic; Molecular Biology/RNA-Protein Interactions; Mutation; Nucleic Acid Conformation; Nucleotides; Oncology/Lung Cancer; Polymorphism; Polymorphism, Single Nucleotide; Protein structure; Ribonucleic acid; RNA; RNA, Ribosomal - genetics; rRNA 45S; Secondary structure; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Structural stability; Transcription; Transcription (Genetics); Transcription, Genetic; Tumor cell lines; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007505

Ribosomal RNA (rRNA) is a central regulator of cell growth and may control cancer development. A cis noncoding rRNA (nc-rRNA) upstream from the 45S rRNA transcription start site has recently been implicated in control of rRNA transcription in mouse fibroblasts. We investigated whether a similar nc-rRNA might be expressed in human cancer epithelial cells, and related to any genomic characteristics. Using quantitative rRNA measurement, we demonstrated that a nc-rRNA is transcribed in human lung epithelial and lung cancer cells, starting from approximately -1000 nucleotides upstream of the rRNA transcription start site (+1) and extending at least to +203. This nc-rRNA was significantly more abundant in the majority of lung cancer cell lines, relative to a nontransformed lung epithelial cell line. Its abundance correlated negatively with total 45S rRNA in 12 of 13 cell lines (P = 0.014). During sequence analysis from -388 to +306, we observed diverse, frequent intercopy single nucleotide polymorphisms (SNPs) in rRNA, with a frequency greater than predicted by chance at 12 sites. A SNP at +139 (U/C) in the 5' leader sequence varied among the cell lines and correlated negatively with level of the nc-rRNA (P = 0.014). Modelling of the secondary structure of the rRNA 5'-leader sequence indicated a small increase in structural stability due to the +139 U/C SNP and a minor shift in local configuration occurrences. The results demonstrate occurrence of a sense nc-rRNA in human lung epithelial and cancer cells, and imply a role in regulation of the rRNA gene, which may be affected by a +139 SNP in the 5' leader sequence of the primary rRNA transcript.