NORAD, a critical long non-coding RNA in human cancers

Soghli, Negin; Yousefi, Tooba; Abolghasemi, Maryam; Qujeq, Durdi

doi:10.1016/j.lfs.2020.118665

Cited by 54 publications

(42 citation statements)

References 65 publications

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“…NORAD is a critical regulator of genome stability. Moreover, human NORAD is dysregulated in various types of cancer and could be an excellent diagnostic or therapeutic biomarker in tumour cells [30] . Since lncRNAs have no protein-coding potential, their structure may be key for exploring their functionality.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, NORAD acts as a competitive endogenous RNA (ceRNA) and regulates cancer progression by sponging MicroRNAs (miRNAs) [29] , [30] . MiRNAs are small regulatory RNAs of about ∼20 nt in length that play critical regulatory roles in eukaryotic cells where they mediate post-transcriptional silencing of specific genes [31] , [32] , [33] .…”

Section: Introductionmentioning

confidence: 99%

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Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units

Chorostecki

Saus

Gabaldón

2021

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units

Chorostecki

Saus

Gabaldón

2021

Computational and Structural Biotechnology Journal

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show abstract

“…NORAD is a critical regulator of genome stability. Moreover, human NORAD is dysregulated in various types of cancer and could be an excellent diagnostic or therapeutic biomarker in tumour cells [26]. Since lncRNAs have no protein-coding potential, their structure may be key for exploring their functionality.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, NORAD acts as a competitive endogenous RNA (ceRNA) and regulates cancer progression by sponging MicroRNAs (miRNAs) [25,26]. MiRNAs are small regulatory RNAs of about ~20 nt in length that play critical regulatory roles in eukaryotic cells where they mediate post-transcriptional silencing of specific genes [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units

Chorostecki

Saus

Gabaldón

2021

Preprint

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Long non-coding RNAs (lncRNAs) can perform a variety of key cellular functions by interacting with proteins and other RNAs. Recent studies have shown that the function of lncRNAS are largely mediated by their structures. However, our structural knowledge for most lncRNAS is limited to sequence-based computational predictions. Non-coding RNA activated by DNA damage (NORAD) is an atypical lncRNA due to its abundant expression and high sequence conservation. NORAD regulates genomic stability by interacting with proteins and microRNAs. Previous sequence-based characterization has identified a modular organization of NORAD composed of several NORAD repeat units (NRUs). These units comprise the protein-binding elements and are separated by regular spacers of unknown function. Here, we experimentally determine for the first time the secondary structure of NORAD using the nextPARS approach. Our results suggest that the spacer regions provide structural stability to NRUs. Furthermore, we uncover two previously-unreported NRUs, and determine the core structural motifs conserved across NRUs. Overall, these findings will help to elucidate the function and evolution of NORAD.

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“…Many of the well-studied lncRNAs, that are considered as regulatory molecules with various significant functions in cancer, have no junctions in their sequences such as MALAT1 , NKILA , NEAT1 and NORAD [ 8 , 9 , 10 , 11 ] ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Genomic DNA Contamination on the Detection of Circulating Long Non-Coding RNAs: The Paradigm of MALAT1

et al. 2021

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The presence of contaminating gDNA in RNA preparations is a frequent cause of false positives in RT-PCR-based analysis. However, in some cases, this cannot be avoided, especially when there are no exons–intron junctions in the lncRNA sequences. Due to the lack of exons in few of long noncoding RNAs (lncRNAs) and the lack of DNAse treatment step in most studies reported so far, serious questions are raised about the specificity of lncRNA detection and the potential of reporting false-positive results. We hypothesized that minute amounts of gDNA usually co-extracted with RNA could give false-positive signals since primers would specifically bind to gDNA due to the lack of junction. In the current study, we evaluated the effect of gDNA and other forms of DNA like extrachromosomal circular DNAs (eccDNAs) contamination and the importance of including a DNAse treatment step on lncRNAsexpression.As a model, we have chosen as one of the most widely studied lncRNAs in cancer namely MALAT1, which lacks exons. When we tested this hypothesis in plasma and primary tissue samples from NSCLC patients, our findings clearly indicated that results on MALAT1 expression are highly affected by the presence of DNA contamination and that the DNAse treatment step is absolutely necessary to avoid false positive results.

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NORAD, a critical long non-coding RNA in human cancers

Cited by 54 publications

References 65 publications

Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units

Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units

Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units

The Effect of Genomic DNA Contamination on the Detection of Circulating Long Non-Coding RNAs: The Paradigm of MALAT1

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