Long Noncoding RNAs at the Crossroads of Cell Cycle and Genome Integrity

The mechanisms by which epigenetic modifications are established in gene regulatory regions of active genes remain poorly understood. The data presented show that the establishment and recycling of a major epigenetic mark, the acetylated form of the replacement histone H2A.Z, is regulated by cell cycle-specific long noncoding RNAs encoded in regions adjacent to the promoters of active genes. These transcripts, termed SPEARs (S Phase EArly RNAs), are induced in early S phase: their expression precedes that of the downstream genes on which they exert their regulatory action. SPEARs drive the modification and deposition of the acetylated form of histone H2A.Z by bringing together the replacement histone and the histone acetyl transferase TIP60. This widespread bimodal pathway constitutes a novel RNA-mediated mechanism for the establishment of epigenetic marks and cell-specific epigenetic profiles, thereby providing a unifying explanation for the accuracy and persistence of epigenetic marks on chromatin.

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Long Noncoding RNA Rps4l Mediates the Proliferation of Hypoxic Pulmonary Artery Smooth Muscle Cells

Hypertension ◽

10.1161/hypertensionaha.120.14644 ◽

2020 ◽

Vol 76 (4) ◽

pp. 1124-1133 ◽

Cited By ~ 1

Author(s):

Ying Liu ◽

Hongyue Zhang ◽

Yiying Li ◽

Lixin Yan ◽

Wei Du ◽

...

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Vascular Remodeling ◽

Cell Cycle Progression ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Cycle Progression ◽

Pulmonary Artery Smooth Muscle

Pulmonary hypertension (PH) is a rare and fatal disorder involving the vascular remodeling of pulmonary arteries mediated by the enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Long noncoding RNAs are a subclass of regulatory molecules with diverse cellular functions, but their role in PH remains largely unexplored. We aimed to identify and determine the functions of long noncoding RNAs involved in hypoxia-induced PH and PASMC proliferation. RNA sequencing in a hypoxic mouse model identified hypoxia-regulated long noncoding RNAs, including Rps4l. Rps4l expression was significantly reduced in PH-model mice and hypoxic PASMCs. The subcellular localization of Rps4l was detected by RNA fluorescence in situ hybridization and quantification of nuclear/cytoplasmic RNA. Rps4l overexpression rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. At the cellular level, Rps4l overexpression weakened cell viability and proliferation and suppressed cell cycle progression. Potential Rps4l-binding proteins were identified via RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, and microscale thermophoresis. These results indicated that Rps4l is associated with and affects the stabilization of ILF3 (interleukin enhancer-binding factor 3). Rps41 further regulates the levels of HIF-1α and consequently leads to hypoxia-induced PASMC proliferation and migration. Our results showed that in hypoxic PASMCs, Rps4l expression decreases due to regulation by hypoxia. This decrease affects the proliferation, migration, and cell cycle progression of PASMCs through ILF3/HIF-1α. These results provide a theoretical basis for further investigations into the pathological mechanism of hypoxic PH and may provide insight for the development of novel treatments.

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Discovery, Annotation, and Functional Analysis of Long Noncoding RNAs Controlling Cell-Cycle Gene Expression and Proliferation in Breast Cancer Cells

Molecular Cell ◽

10.1016/j.molcel.2015.06.023 ◽

2015 ◽

Vol 59 (4) ◽

pp. 698-711 ◽

Cited By ~ 95

Author(s):

Miao Sun ◽

Shrikanth S. Gadad ◽

Dae-Seok Kim ◽

W. Lee Kraus

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cell Cycle ◽

Functional Analysis ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Cell Cycle Gene ◽

Cell Cycle Gene Expression

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Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

Oncology Letters ◽

10.3892/ol.2016.5288 ◽

2016 ◽

Vol 12 (6) ◽

pp. 4605-4612 ◽

Cited By ~ 10

Author(s):

Ping Wang ◽

Jiayue Cui ◽

Jihong Wen ◽

Yunhui Guo ◽

Liangzi Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Signaling Pathway ◽

Hepg2 Cell ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

P53 Signaling ◽

Cycle Arrest ◽

P53 Signaling Pathway

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Role of MYC-Regulated Long Noncoding RNAs in Cell Cycle Regulation and Tumorigenesis

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/dju505 ◽

2015 ◽

Vol 107 (4) ◽

Cited By ~ 81

Author(s):

Taewan Kim ◽

Young-Jun Jeon ◽

Ri Cui ◽

Ji-Hoon Lee ◽

Yong Peng ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Regulation ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Cycle Regulation

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Formation and recycling of an active epigenetic mark mediated by cell cycle-specific RNAs

10.21203/rs.3.rs-464637/v1 ◽

2021 ◽

Author(s):

Daniel Tenen ◽

Alexander Ebralidze ◽

Vladimir Angarica ◽

Yanjing Liu ◽

Dennis Kappei ◽

...

Keyword(s):

Cell Cycle ◽

Noncoding Rnas ◽

S Phase ◽

Long Noncoding Rnas ◽

Epigenetic Mark ◽

Histone Acetyl Transferase ◽

Regulatory Regions ◽

Epigenetic Marks ◽

Gene Regulatory ◽

Active Genes

Abstract The mechanisms by which epigenetic modifications are established in gene regulatory regions of active genes remain poorly understood. The data presented show that the establishment and recycling of a major epigenetic mark, the acetylated form of the replacement histone H2A.Z, is regulated by cell cycle-specific long noncoding RNAs encoded in regions adjacent to the promoters of active genes. These transcripts, termed SPEARs (S Phase EArly RNAs), are induced in early S phase: their expression precedes that of the downstream genes on which they exert their regulatory action. SPEARs drive the modification and deposition of the acetylated form of histone H2A.Z by bringing together the replacement histone and the histone acetyl transferase TIP60. This widespread bimodal pathway constitutes a novel RNA-mediated mechanism for the establishment of epigenetic marks and cell-specific epigenetic profiles, thereby providing a unifying explanation for the accuracy and persistence of epigenetic marks on chromatin.

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MYC-repressed long noncoding RNAs antagonize MYC-induced cell proliferation and cell cycle progression

Oncotarget ◽

10.18632/oncotarget.3909 ◽

2015 ◽

Vol 6 (22) ◽

pp. 18780-18789 ◽

Cited By ~ 38

Author(s):

Taewan Kim ◽

Ri Cui ◽

Young-Jun Jeon ◽

Paolo Fadda ◽

Hansjuerg Alder ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Cycle Progression

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Screening of Long Noncoding RNAs Induced by Radiation Using Microarray

Dose-Response ◽

10.1177/1559325820916304 ◽

2020 ◽

Vol 18 (2) ◽

pp. 155932582091630

Author(s):

Yilong Wang ◽

Qi Wang ◽

Shuangjing Chen ◽

Yingchun Hu ◽

Chang Yu ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Messenger Rna ◽

Target Genes ◽

Noncoding Rnas ◽

A549 Cells ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Damage Repair ◽

Mcf 7

DNA damage repair and G2/M arrest are the key factors regulating the survival of cancer cells exposed to radiation. Recent studies have shown that long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes, including DNA repair, cell cycle regulation, differentiation, and epigenetic regulation. However, the knowledge about the genome scale of lncRNAs and their potential biological functions in tumor cells exposed to radiation are still unclear. In this study, we used LncRNA + mRNA Human Gene Expression Microarray V4.0 to profile lncRNA and messenger RNA (mRNA) from HeLa, MCF-7, and A549 cells after irradiation with 4 Gy of γ-radiation. We identified 230, 227, and 274 differentially expressed lncRNAs and 150, 214, and 274 differentially expressed mRNAs in HeLa, MCF-7, and A549 cells, respectively, among which there are 14 common differentially expressed lncRNAs and 22 common differentially expressed mRNAs in all of the 3 cell lines. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these differentially expressed mRNAs were mainly associated with cell cycle. Further, we also predicted the target genes and functions of these differentially expressed lncRNAs. Our study on lncRNAs has greatly expanded the field of gene research in the relationship of radiation, cell cycle, and DNA damage.

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