Long non-coding RNAs: insights into functions

Mercer, Tim R.; Dinger, Marcel E.; Mattick, John S.

doi:10.1038/nrg2521

Cited by 4,964 publications

(3,880 citation statements)

References 48 publications

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“…Because the half-lives of nascent transcripts are generally much shorter than those of mRNA (Griffiths-Jones, 2007; Mattick, 2009; Mercer et al, 2009; Wang and Chang, 2011), a short burst of transcription can result in elevated mRNA expression that lasts several hours, as has been shown in systems involving an acute inflammatory response (Cheadle et al, 2005; Hao and Baltimore, 2009). However, generic mRNA stability cannot account for this buffering, as many genes with arrhythmic but variable transcription do not exhibit rhythmic mRNA expression (Figure 6H).…”

Section: Discussionmentioning

confidence: 99%

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Menet

Rodriguez

Abruzzi

et al. 2012

eLife

285

401

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A substantial fraction of the metazoan transcriptome undergoes circadian oscillations in many cells and tissues. Based on the transcription feedback loops important for circadian timekeeping, it is commonly assumed that this mRNA cycling reflects widespread transcriptional regulation. To address this issue, we directly measured the circadian dynamics of mouse liver transcription using Nascent-Seq (genome-wide sequencing of nascent RNA). Although many genes are rhythmically transcribed, many rhythmic mRNAs manifest poor transcriptional rhythms, indicating a prominent contribution of post-transcriptional regulation to circadian mRNA expression. This analysis of rhythmic transcription also showed that the rhythmic DNA binding profile of the transcription factors CLOCK and BMAL1 does not determine the transcriptional phase of most target genes. This likely reflects gene-specific collaborations of CLK:BMAL1 with other transcription factors. These insights from Nascent-Seq indicate that it should have broad applicability to many other gene expression regulatory issues.DOI: http://dx.doi.org/10.7554/eLife.00011.001

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Section: Discussionmentioning

confidence: 99%

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Menet

Rodriguez

Abruzzi

et al. 2012

eLife

285

401

View full text Add to dashboard Cite

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“…Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and ability to local or global regulation of gene expression via epigenetic, transcriptional or post-transcriptional mechanisms [3]. Indeed, several lncRNAs were found to have crucial roles in controlling cellular pathways and gene expression programs, thus impacting the oncogenic processes by presenting either oncogenic or tumor suppressive functions [4].…”

Section: Introductionmentioning

confidence: 99%

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

et al. 2017

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restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.

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“…Mature miRNAs are incorporated into the RNA‐induced silencing complex to mediate the transcriptional or post‐transcriptional regulation of gene expression by binding to the 3′‐untranslated regions (3′‐UTR) of the target mRNA 3, 4. Recently, another class of ncRNAs, the long noncoding RNAs (lncRNAs) have gained increased attention 5, 6. Unlike the miRNAs, lncRNAs are longer, more than 200nt in length and usually have complex and diverse sequences.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

Guo

Jiang

et al. 2015

J Cellular Molecular Medi

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Recently, rapid advances in bioinformatics analysis have expanded our understanding of the transcriptome to a genome‐wide level. miRNA–mRNA–lncRNA interactions have been shown to play critical regulatory role in cancer biology. In this study, we discussed the use of an integrated systematic approach to explore new facets of the oestrogen receptor (ER)‐regulated transcriptome. The identification of RNAs that are related to the expression status of the ER may be useful in clinical therapy and prognosis. We used a network modelling strategy. First, microarray expression profiling of mRNA, lncRNA and miRNA was performed in MCF‐7 (ER‐positive) and MDA‐MB‐231 cells (ER‐ negative). A co‐expression network was then built using co‐expression relationships of the differentially expressed mRNAs and lncRNAs. Finally, the selected miRNA–mRNA network was added to the network. The key miRNA–mRNA–lncRNA interaction can be inferred from the network. The mRNA and non‐coding RNA expression profiles of the cells with different ER phenotypes were distinct. Among the aberrantly expressed miRNAs, the expression levels of miR‐19a‐3p, miR‐19b‐3p and miR‐130a‐3p were much lower in the MCF‐7 cells, whereas that of miR‐148b‐3p was much higher. In a cluster of miR‐17‐92, the expression levels of six of seven miRNAs were lower in the MCF‐7 cells, in addition to miR‐20b in the miR‐106a‐363 cluster. However, the levels of all the miRNAs in the miR‐106a‐25 cluster were higher in the MCF‐7 cells. In the co‐expression networking, CD74 and FMNL2 gene which is involved in the immune response and metastasis, respectively, had a stronger correlation with ER. Among the aberrantly expressed lncRNAs, lncRNA‐DLEU1 was highly expressed in the MCF‐7 cells. A statistical analysis revealed that there was a co‐expression relationship between ESR1 and lncRNA‐DLEU1. In addition, miR‐19a and lncRNA‐DLEU1 are both located on the human chromosome 13q. We speculate that miR‐19a might be co‐expressed with lncRNA‐DLEU1 to co‐regulate the expression of ESR1, which influences the occurrence and development of breast cancer cells with different levels of ER expression. Our findings reveal that the status of ER is mainly due to the differences in the mRNA and ncRNA profile between the breast cancer cell lines, and highlight the importance of studying the miRNA–mRNA–lncRNA interactions to completely illustrate the intricate transcriptome.

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Long non-coding RNAs: insights into functions

Cited by 4,964 publications

References 48 publications

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

Analysis of the miRNA–mRNA–lncRNA networks in ER+ and ER− breast cancer cell lines

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