Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins

Rackham, Oliver; Shearwood, Anne-Marie J.; Mercer, Tim R.; Davies, Stefan M.K.; Mattick, John S.; Filipovska, Aleksandra

doi:10.1261/rna.029405.111

Cited by 275 publications

(240 citation statements)

References 34 publications

Supporting

Mentioning

221

Contrasting

Unclassified

Order By: Relevance

“…The author indicates that several groups have reported the presence of miRNAs in the mitochondria and their relationship with cancer [32,33]. This review also describes the finding of mitochondrial lncRNAs in different cell types such as HeLa cells, breast cells and ventricular tissue [34,35,36], fulfilling different roles as regulators of translation or as novel biomarkers of disease progression. Among these, LIPCAR (Long Intergenic noncoding RNA Predicting CARdiac remodeling) is worthy of mention, as it is upregulated at late stages of left ventricular remodeling and is elevated in patients with chronic heart failure, suggesting this mtlncRNA as a prognostic indicator for cardiovascular mortality [37].…”

Section: Discussionmentioning

confidence: 98%

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Dadlani¹,

López²,

Fern³

et al. 2016

J Cancer Sci Ther

View full text Add to dashboard Cite

Objective: Cervical cancer is the second most common cancer in women with high rates of mortality worldwide. Cervical cancer is slowly progressive and is preceded by pre-invasive intraepithelial lesions. Therefore, detection of premalignant lesions is key to preventing disease progression to advanced stages. The objective of the present study was examination and quantification of the differentially expressed non-coding mitochondrial RNAs during progression of disease. Material and methods:The differential expression of S-ncmtRNA and AS-ncmtRNA was analyzed by in situ hybridization (ISH) using tissue macroarrays (TMA) from normal, CIN1, CIN2, CIN3 and invasive squamous carcinoma (SCC). PCNA and p16INK-4a were detected in consecutive biopsies by immunohistochemistry. Quantification of ISH signal was carried out with Image ProPlus 6.1 software and the results were expressed as percentage of Integrated Optical Density (IOD). Results:We found a marked down-regulation of AS-ncmtRNA in 95% of tissues analyzed (CIN 1/2, CIN 3, and invasive squamous cancer). Moreover, differential expression of ASncmtRNA v/s S-ncmtRNA showed significant difference. Normal proliferating tissues did not display down-regulation of AS-ncmtRNA. Down regulation of ASncmtRNA correlated with the expression of the tumor suppressor protein p16INK-4a Conclusions:We found down-regulation of AS-ncmtRNA in pre-malignant and tumor samples which could distinguish normal tissues from early lesions and tumor samples. These results suggest that the down-regulation of AS-ncmtRNA is a novel marker of early lesions and cervix neoplasia. Previously, we reported that human cells express a unique family of mitochondrial long ncmtRNAs (ncmtRNAs) [12,13]. One of these transcripts, named sense ncmtRNA (SncmtRNA) is expressed in normal proliferating cells and tumor cells but not in resting cells, suggesting a functional role in cell cycle progression [12]. Normal proliferating cells express, in addition to the S-ncmtRNA, two antisense mitochondrial ncmtRNAs (AS-ncmtRNA-1 and AS-ncmtRNA-2) where both AS-ncmtRNAs are down-regulated in human cancer cells regardless of tissue of origin. In order to analyze the expression pattern of these ncmtRNAs in cervical cancer, we performed a qualitative pilot study in cervical biopsies encompassing the progression of the disease. We found that AS-ncmtRNAs are down-regulated in mild, moderate and severe neoplasia and in invasive cervical carcinoma [14]. In the present study a quantitative analysis of the differential expression of the S-ncmtRNA and the ASncmtRNAs was performed in biopsies of CIN1 to CIN3 and invasive cervical carcinoma, correlating it with the expression of the tumor suppressor p16 Assessment of the Expression of LongINK 4A and proliferating cell nuclear antigen (PCNA). Methods Tissue specimensAll the tissues were purchased from Pantomics Inc. (Richmond, CA, USA), corresponding to Tissue Macroarrays (TMA) containing normal cervix, CIN1, CIN2, CIN3 and invasive squamous carcinoma (SCC). For normal specimens,...

show abstract

Section: Discussionmentioning

confidence: 98%

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Dadlani¹,

López²,

Fern³

et al. 2016

J Cancer Sci Ther

View full text Add to dashboard Cite

show abstract

“…To date, the mechanism of ASncmtRNA-1 and ASncmtRNA-2 remains unknown (De Paepe et al 2017;). Three lncRNAs: ncND5, lncND6, and lncCyt b were identified as antisense transcripts of the mtND5, mtND6, and mtCYTB mRNAs but little is known about their function (Rackham, et al 2011). …”

Section: Mitochondrial-encoded Lncrnas and Lncrna Imported Into Mitocmentioning

confidence: 99%

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

Klinge

2018

Endocrine-Related Cancer

View full text Add to dashboard Cite

Abstract:The human genome is 'pervasively transcribed' leading to a complex array of noncoding RNAs (ncRNAs) that far outnumber coding mRNAs. ncRNAs have regulatory roles in transcription and post-transcriptional processes as well numerous cellular functions that remain to be fully described. Best characterized of the 'expanding universe' of ncRNAs are the ~ 22 nucleotide microRNAs (miRNAs) that base-pair to target mRNA's 3' untranslated region within the RNA-induced silencing complex (RISC) and block translation and may stimulate mRNA transcript degradation. Long non-coding RNAs (lncRNAs) are classified as >200 nucleotides in length, but range up to several kb and are heterogeneous in genomic origin and function.LncRNAs fold into structures that interact with DNA, RNA, and proteins to regulate chromatin dynamics, protein complex assembly, transcription, telomere biology, and splicing. Some lncRNAs act as sponges for miRNAs and decoys for proteins. Nuclear-encoded lncRNAs can be taken up by mitochondria and lncRNAs are transcribed from mtDNA. Both miRNAs and lncRNAs are dysregulated in endocrine cancers. This review provides an overview on the current understanding of the regulation and function of selected lncRNAs and miRNAs, and their interaction, in endocrine-related cancers: breast, prostate, endometrial, and thyroid.

show abstract

“…Coevolution of both DNAs is a fundamental process that preserves biological functionality and cell activity (51). Interaction between nDNA and mtDNA products is known to occur at different levels such as protein-protein interaction in oxidative phosphorylation (OXPHOS), protein-RNA interactions, and nuclear factor-mtDNA recognition sites interactions in the processes of replication and transcription (3,63,77). Epigenetic changes play a role in this cross talk being both instrument and recipient of informative flows between the two genomes.…”

Section: Epigenetic Cross Talk At the Dna Levelmentioning

confidence: 99%

The mitochondrial side of epigenetics

Castegna

Iacobazzi

Infantino

2015

Physiological Genomics

View full text Add to dashboard Cite

The bidirectional cross talk between nuclear and mitochondrial DNA is essential for cellular homeostasis and proper functioning. Mitochondria depend on nuclear contribution for much of their functionality, but their activities have been recently recognized to control nuclear gene expression as well as cell function in many different ways. Epigenetic mechanisms, which tune gene expression in response to environmental stimuli, are key regulatory events at the interplay between mitochondrial and nuclear interactions. Emerging findings indicate that epigenetic factors can be targets or instruments of mitochondrial-nuclear cross talk. Additionally, the growing interest into mtDNA epigenetic modifications opens new avenues into the interaction mechanisms between mitochondria and nucleus. In this review we summarize the points of mitochondrial and nuclear reciprocal control involving epigenetic factors, focusing on the role of mitochondrial genome and metabolism in shaping epigenetic modulation of gene expression. The relevance of the new findings on the methylation of mtDNA is also highlighted as a new frontier in the complex scenario of mitochondrial-nuclear communication.

show abstract

Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins

Cited by 275 publications

References 34 publications

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

The mitochondrial side of epigenetics

Contact Info

Product

Resources

About