Expression of a novel non-coding mitochondrial RNA in human proliferating cells

Villegas, Jaime; Burzio, Verónica A.; Villota, Claudio; Landerer, Eduardo; Martínez, Ronny; Santander, Marcela; Martinez, Rodrigo; Pinto, Rodrigo; Vera, María; Boccardo, Enrique; Villa, Luisa L.; Burzio, Luis O.

doi:10.1093/nar/gkm863

Cited by 80 publications

(157 citation statements)

References 56 publications

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“…1B, Right). A similar expression pattern was obtained with 8 additional tumor cell lines (2). The normal proliferating cells HUVEC, HFK, and HUTEC also express this transcript (Fig.…”

Section: Resultssupporting

confidence: 80%

“…R ecently, we described a novel human mitochondrial transcript of 2,374 nt that contains a long inverted repeat (IR) linked to the 5Ј end of the 16S mitochondrial rRNA (16S mtrRNA) (1, 2), which we designated noncoding mitochondrial RNA or ncmtRNA (2). The IR generates a stem-loop structure with an 820-bp doublestranded region and a 40-nt loop (2).…”

mentioning

confidence: 99%

“…The IR generates a stem-loop structure with an 820-bp doublestranded region and a 40-nt loop (2). In situ hybridization (ISH) showed that the ncmtRNA is overexpressed in several tumor cell lines but not in nondividing cells, suggesting that the ncmtRNA may play a role in cell proliferation (2).…”

mentioning

confidence: 99%

“…However, and in striking contrast with tumor cell lines, ISH of normal proliferating cells revealed expression of antisense transcripts. These molecules were identified as 2 unique transcripts containing IRs linked to the 5Ј region of the antisense 16S mtRNA transcribed from the L-strand of the mtDNA (1,2). We named these transcripts antisense ncmtRNA-1 (ASncmtRNA-1) and antisense ncmtRNA-2 (ASncmtRNA-2).…”

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confidence: 99%

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Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells

Burzio

Villota

Villegas

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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116

198

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We reported the presence in human cells of a noncoding mitochondrial RNA that contains an inverted repeat (IR) of 815 nucleotides (nt) covalently linked to the 5 end of the mitochondrial 16S RNA (16S mtrRNA). The transcript contains a stem-loop structure and is expressed in human proliferating cells but not in resting cells. Here, we demonstrate that, in addition to this transcript, normal human proliferating cells in culture express 2 antisense mitochondrial transcripts. These transcripts also contain stem-loop structures but strikingly they are down-regulated in tumor cell lines and tumor cells present in 17 different tumor types. The differential expression of these transcripts distinguishes normal from tumor cells and might contribute a unique vision on cancer biology and diagnostics.differential expression in cancer ͉ RNAs with stem-loop structures R ecently, we described a novel human mitochondrial transcript of 2,374 nt that contains a long inverted repeat (IR) linked to the 5Ј end of the 16S mitochondrial rRNA (16S mtrRNA) (1, 2), which we designated noncoding mitochondrial RNA or ncmtRNA (2). The IR generates a stem-loop structure with an 820-bp doublestranded region and a 40-nt loop (2). In situ hybridization (ISH) showed that the ncmtRNA is overexpressed in several tumor cell lines but not in nondividing cells, suggesting that the ncmtRNA may play a role in cell proliferation (2).Because the results described before were obtained using tumor cell lines (2), we asked whether the ncmtRNA (from now on, sense ncmtRNA, SncmtRNA) is expressed in normal proliferating cells. Here we show that ISH of human umbilical vein endothelial cells (HUVEC), foreskin keratinocytes (HFK) (3), and human tonsil endothelial cells (HUTEC) (4) also express the SncmtRNA. However, and in striking contrast with tumor cell lines, ISH of normal proliferating cells revealed expression of antisense transcripts. These molecules were identified as 2 unique transcripts containing IRs linked to the 5Ј region of the antisense 16S mtRNA transcribed from the L-strand of the mtDNA (1, 2). We named these transcripts antisense ncmtRNA-1 (ASncmtRNA-1) and antisense ncmtRNA-2 (ASncmtRNA-2). Finally, we show that the antisense transcripts are also expressed in proliferating cells present in normal human tissues but are down-regulated in cells present in human tumors of different types and patients.

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“…1B, Right). A similar expression pattern was obtained with 8 additional tumor cell lines (2). The normal proliferating cells HUVEC, HFK, and HUTEC also express this transcript (Fig.…”

Section: Resultssupporting

confidence: 80%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells

Burzio

Villota

Villegas

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

116

198

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“…Later the same workers demonstrated that human cells contain a transcript of 2374 nt with similar structural features to the mouse mtRNA. This transcript contained a stem-loop structure with an 820-bp double-stranded region and a 40-nt loop, and that it was expressed in human proliferating cells but not in resting cells, suggesting that this ncmtRNA may play a role in cell proliferation [73]. Recently, Burzio et al [74] reported that in addition to this transcript, normal human proliferating cells in culture expressed two ncmtRNA transcripts, sense ncmtRNA (SncmtRNA) and antisense ncmtRNA (ASncmtRNA).…”

Section: Noncoding Mitochondrial Rnasmentioning

confidence: 99%

Noncoding RNAs: Different roles in tumorigenesis

Lin

2012

Chin. Sci. Bull.

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A major portion of the mammalian genome is transcribed to produce large numbers of noncoding RNAs (ncRNAs). During the past decade, the discovery of small RNAs, including the microRNAs (miRNA) and small interfering RNAs (siRNA), has led to important advances in biology. The breadth of the ncRNA field of study has substantially expanded and many recent results have revealed a range of functions that can be attributed to the miRNAs and other ncRNAs. For example, H19 RNA, HOTAIR RNA, transcribed ultraconserved regions (T-UCRs), natural antisense RNA, transfer RNA and mitochondrial noncoding RNA have been suggested to play important roles in cancers and other diseases as well as in diverse cellular processes. In this review, we focus on the current status of several classes of ncRNAs associated with cancer with the emphasis on those that are not microRNAs. Mounting evidence has revealed that a major portion of the mammalian genome is transcribed to produce large numbers of noncoding RNAs (ncRNAs), that is, RNAs that either do not have an open reading frame or RNAs that have a short poorly conserved open reading frame and do not code for a protein [1,2]. During the past decade, the discovery of small RNAs including the microRNAs (miRNAs) and small interfering RNAs (siRNAs) has led to major advances in biology. After miRNAs were first connected to cancer pathogenesis [3], accumulating data have pointed to a central regulatory role for miRNAs in the initiation and progression of most of the cancers that have been analyzed so far. Recently, the breadth of the ncRNA field of study has substantially expanded. A series of studies have revealed the essential roles of many ncRNAs in diverse cellular processes including cancer; these ncRNAs include H19 RNA, HOTAIR RNA, transcribed ultraconserved regions (T-UCRs), natural antisense RNA, transfer RNA and mitochondrial noncoding RNA (Figure 1). In this review, we focus on the current status of the research into the several classes of ncRNAs associated with cancer.

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Mitochondrial DNA: Epigenetics and environment

Sharma

Pasala

Prakash

2019

Environ and Mol Mutagen

120

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Maintenance of the mitochondrial genome is essential for proper cellular function. For this purpose, mitochondrial DNA (mtDNA) needs to be faithfully replicated, transcribed, translated, and repaired in the face of constant onslaught from endogenous and environmental agents. Although only 13 polypeptides are encoded within mtDNA, the mitochondrial proteome comprises over 1500 proteins that are encoded by nuclear genes and translocated to the mitochondria for the purpose of maintaining mitochondrial function. Regulation of mtDNA and mitochondrial proteins by epigenetic changes and post‐translational modifications facilitate crosstalk between the nucleus and the mitochondria and ultimately lead to the maintenance of cellular health and homeostasis. DNA methyl transferases have been identified in the mitochondria implicating that methylation occurs within this organelle; however, the extent to which mtDNA is methylated has been debated for many years. Mechanisms of demethylation within this organelle have also been postulated, but the exact mechanisms and their outcomes is still an active area of research. Mitochondrial dysfunction in the form of altered gene expression and ATP production, resulting from epigenetic changes, can lead to various conditions including aging‐related neurodegenerative disorders, altered metabolism, changes in circadian rhythm, and cancer. Here, we provide an overview of the epigenetic regulation of mtDNA via methylation, long and short noncoding RNAs, and post‐translational modifications of nucleoid proteins (as mitochondria lack histones). We also highlight the influence of xenobiotics such as airborne environmental pollutants, contamination from heavy metals, and therapeutic drugs on mtDNA methylation. Environ. Mol. Mutagen., 60:668–682, 2019. © 2019 Wiley Periodicals, Inc.

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Expression of a novel non-coding mitochondrial RNA in human proliferating cells

Cited by 80 publications

References 56 publications

Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells

Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells

Noncoding RNAs: Different roles in tumorigenesis

Mitochondrial DNA: Epigenetics and environment

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