An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.

<h4>Background</h4>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 inve...

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Main Authors: Yih-Horng Shiao, Sorin T Lupascu, Yuhan D Gu, Wojciech Kasprzak, Christopher J Hwang, Janet R Fields, Robert M Leighty, Octavio Quiñones, Bruce A Shapiro, W Gregory Alvord, Lucy M Anderson
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Language:English
Published: Public Library of Science (PLoS) 2009-10-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007505&type=printable
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author Yih-Horng Shiao
Sorin T Lupascu
Yuhan D Gu
Wojciech Kasprzak
Christopher J Hwang
Janet R Fields
Robert M Leighty
Octavio Quiñones
Bruce A Shapiro
W Gregory Alvord
Lucy M Anderson
author_facet Yih-Horng Shiao
Sorin T Lupascu
Yuhan D Gu
Wojciech Kasprzak
Christopher J Hwang
Janet R Fields
Robert M Leighty
Octavio Quiñones
Bruce A Shapiro
W Gregory Alvord
Lucy M Anderson
author_sort Yih-Horng Shiao
collection DOAJ
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
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spelling doaj-art-8f2e7461c53b47b7b36b8ffa0babccbc2025-08-20T02:01:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e750510.1371/journal.pone.0007505An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.Yih-Horng ShiaoSorin T LupascuYuhan D GuWojciech KasprzakChristopher J HwangJanet R FieldsRobert M LeightyOctavio QuiñonesBruce A ShapiroW Gregory AlvordLucy M Anderson<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007505&type=printable
spellingShingle Yih-Horng Shiao
Sorin T Lupascu
Yuhan D Gu
Wojciech Kasprzak
Christopher J Hwang
Janet R Fields
Robert M Leighty
Octavio Quiñones
Bruce A Shapiro
W Gregory Alvord
Lucy M Anderson
An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.
PLoS ONE
title An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.
title_full An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.
title_fullStr An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.
title_full_unstemmed An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.
title_short An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.
title_sort intergenic non coding rrna correlated with expression of the rrna and frequency of an rrna single nucleotide polymorphism in lung cancer cells
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007505&type=printable
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