Cell cycle regulation by long non-coding RNAs

Thousands of genes encoding long noncoding RNAs (lncRNAs) have been identified in all vertebrate genomes thus far examined. The list of lncRNAs partaking in arguably important biochemical, cellular, and developmental activities is steadily growing. However, it is increasingly clear that lncRNA repertoires are subject to weak functional constraint and rapid turnover during vertebrate evolution. Here we discuss some of the factors that may explain this apparent paradox, including relaxed constraint on sequence to maintain lncRNA structure/function, extensive redundancy in the regulatory circuits in which lncRNAs act, as well as adaptive and non-adaptive forces such as genetic drift. We explore the molecular mechanisms promoting the birth and rapid evolution of lncRNA genes with an emphasis on the influence of bidirectional transcription and transposable elements, two pervasive features of vertebrate genomes. Together these properties reveal a remarkably dynamic and malleable noncoding transcriptome, which may represent an important source of robustness and evolvability.

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“…193], circadian clock [e.g. 194], cell cycle regulation [reviewed in 195], pluripotency [e.g. 17, 31, 123], and innate immunity [196].…”

Section: Box 1 Conservation Of Biological Function Despite Low Sequenmentioning

confidence: 99%

Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications

2014

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“…Noncoding RNAs (ncRNAs) comprise a majority of the genome and play important developmental and physiological roles, as well as roles in disease mainly by regulating gene expression 10, 11 . This regulation by ncRNAs can be on proximal genes or distant genes via many mechanisms, including modifying chromatin, controlling transcription, degrading mRNA, and splicing 12 .…”

Section: Introductionmentioning

confidence: 99%

Altered Expression of Long Noncoding RNAs in Blood After Ischemic Stroke and Proximity to Putative Stroke Risk Loci

Dykstra-Aiello

Jickling

Ander

et al. 2016

Stroke

117

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Background and Purpose Though peripheral blood mRNA and microRNA change following ischemic stroke, any role for long noncoding RNA (lncRNA), which comprise most of the genome and have been implicated in various diseases, is unknown. Thus, we hypothesized that lncRNA expression also changes following stroke. Methods lncRNA expression was assessed in 266 whole-blood RNA samples drawn once per individual from ischemic stroke patients and matched vascular risk factor controls. Differential lncRNA expression was assessed by Analysis of Covariance (ANCOVA, p-value < 0.005; fold change > |1.2|), principal components analysis and hierarchical clustering on a derivation set (n=176) and confirmed on a validation set (n=90). Post-stroke temporal lncRNA expression changes were assessed using ANCOVA with confounding factor correction (p<0.005; partial correlation with time since event >|0.4|). Because sexual dimorphism exists in stroke, analyses were performed for each sex separately. Results 299 lncRNAs were differentially expressed between stroke and control males, whereas 97 lncRNAs were differentially expressed between stroke and control females. Significant changes of lncRNA expression with time after stroke were detected for 49 lncRNAs in males and 31 lncRNAs in females. Some differentially expressed lncRNAs mapped close to genomic locations of previously identified putative stroke-risk genes, including Lipoprotein, Lp(A)-Like 2, ABO blood group, Prostaglandin 12 Synthase, and α-Adducins. Conclusions This study provides evidence of altered and sexually dimorphic lncRNA expression in peripheral blood of stroke patients compared to controls and suggests lncRNAs have potential for stroke biomarker development. Some regulated lncRNA could regulate some previously identified putative stroke-risk genes.

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“…Moreover, a genome-wide approach for determining RNA stability, which is called 5'-bromouridine (BrU) immunoprecipitation chase-deep assay (BRIC), or BRIC through deep sequencing (BRIC-Seq) (9)(10)(11), revealed that ncRNAs with short half-lives (RNA half-life t 1/2 < 4 h) included known regulatory ncRNAs, such as HOX transcript antisense RNA (HOTAIR), antisense noncoding RNA in the inhibitors of CDK4 locus (ANRIL)/CDKN2B antisense RNA 1 (CDKN2B-AS1), and growth arrest specific 5 (GAS5). BRIC-Seq has revealed 785 lncRNAs with short half-lives, termed Short-Lived non-coding Transcripts (SLiTs) (9), and I have selected 26 lncRNAs that are short-lived (t 1/2 < 4 h) in HeLa-Tet-off cells (Table 1), longer than 200 nt, and fulfill the established criteria for lncRNA classification.…”

Section: Introductionmentioning

confidence: 99%

Short-lived non-coding transcripts (SLiTs): Clues to regulatory long non-coding RNA

Tani

2017

DD&T

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Cell cycle regulation by long non-coding RNAs

Cited by 217 publications

References 79 publications

Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications

Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications

Altered Expression of Long Noncoding RNAs in Blood After Ischemic Stroke and Proximity to Putative Stroke Risk Loci

Short-lived non-coding transcripts (SLiTs): Clues to regulatory long non-coding RNA

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