Epigenetic Regulation of Noncoding RNA Transcription by Mammalian RNA Polymerase III

Published on Jan 23, 2017in Epigenomics4.112
· DOI :10.2217/EPI-2016-0108
Jong Lyul Park11
Estimated H-index: 11
(Korea Research Institute of Bioscience and Biotechnology),
Young-Jong Lee + 2 AuthorsYong Sun Lee19
Estimated H-index: 19
Sources
Abstract
RNA polymerase III (Pol III) synthesizes a range of medium-sized noncoding RNAs (collectively ‘Pol III genes’) whose early established biological roles were so essential that they were considered ‘housekeeping genes’. Besides these fundamental functions, diverse unconventional roles of mammalian Pol III genes have recently been recognized and their expression must be exquisitely controlled. In this review, we summarize the epigenetic regulation of Pol III genes by chromatin structure, histone modification and CpG DNA methylation. We also recapitulate the association between dysregulation of Pol III genes and diseases such as cancer and neurological disorders. Additionally, we will discuss why in-depth molecular studies of Pol III genes have not been attempted and how nc886, a Pol III gene, may resolve this issue.
📖 Papers frequently viewed together
12 Citations
1 Citations
2 Citations
References110
Newest
#1Qian Zhong (SYSU: Sun Yat-sen University)H-Index: 23
#2Shaoyan Xi (SYSU: Sun Yat-sen University)H-Index: 8
Last. Shuping Zhong (STU: Shantou University)H-Index: 21
view all 8 authors...
// Qian Zhong 1, * , Shaoyan Xi 1, * , Jianzhong Liang 1, * , Ganggang Shi 2 , Yi Huang 3 , Yanmei Zhang 2, 3 , Daniel Levy 3 , Shuping Zhong 2, 3 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China 2 Shantou University Medical College, Shantou, Guangdong, China 3 Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA * These authors have contributed equally to this w...
22 CitationsSource
#1Yu Fu (UTMB: University of Texas Medical Branch)H-Index: 2
#2Inhan LeeH-Index: 2
Last. Xiaoyong BaoH-Index: 1
view all 4 authors...
tRNA-derived RNA fragments (tRFs) are an emerging class of non-coding RNAs (ncRNAs). A growing number of reports have shown that tRFs are not random degradation products but are functional ncRNAs made of specific tRNA cleavage. They play regulatory roles in several biological contexts such as cancer, innate immunity, stress responses, and neurological disorders. In this review, we summarize the biogenesis and functions of tRFs.
26 CitationsSource
#1Jana Koo (St. John's University)H-Index: 2
#2Stephanie Cabarcas-Petroski (PSU: Pennsylvania State University)H-Index: 2
Last. Laura Schramm (St. John's University)H-Index: 16
view all 6 authors...
Background BRF2 is a transcription factor required for synthesis of a small group of non-coding RNAs by RNA polymerase III. Overexpression of BRF2 can transform human mammary epithelial cells. In both breast and lung cancers, the BRF2 gene is amplified and overexpressed and may serve as an oncogenic driver. Furthermore, elevated BRF2 can be independently prognostic of unfavorable survival. Dietary soy isoflavones increase metastasis to lungs in a model of breast cancer and a recent study reporte...
23 CitationsSource
#1Sarina Ravens (UDS: University of Strasbourg)H-Index: 3
#1Sarina Ravens (UDS: University of Strasbourg)H-Index: 14
Last. Laszlo Tora (UDS: University of Strasbourg)H-Index: 81
view all 5 authors...
Background Tip60 (KAT5) is the histone acetyltransferase (HAT) of the mammalian Tip60/NuA4 complex. While Tip60 is important for early mouse development and mouse embryonic stem cell (mESC) pluripotency, the function of Tip60 as reflected in a genome-wide context is not yet well understood.
32 CitationsSource
#1Akshat Khanna (SC: University of Southern California)H-Index: 4
#2Ajay Pradhan (SC: University of Southern California)H-Index: 2
Last. Sean P. Curran (SC: University of Southern California)H-Index: 19
view all 3 authors...
Maf1 was first identified in yeast, and studies in metazoans have primarily focused on examining its role in the repression of transcription that is dependent on RNA polymerase III. Recent work has revealed a novel and conserved function for Maf1 in the maintenance of intracellular lipid pools in Caenorhabditis elegans, mice, and cancer cell lines. Although additional Maf1 targets are likely, they have not been identified, and these recent findings begin to define specific activities for Maf1 in...
16 CitationsSource
#1Chang Liu (PKU: Peking University)H-Index: 104
#1Chang Liu (PKU: Peking University)H-Index: 1
Last. Hongquan Zhang (PKU: Peking University)H-Index: 30
view all 9 authors...
Polycomb repression complex 2 (PRC2) component EZH2 tri-methylates H3K27 and exerts epigenetic repression on target gene expression. EZH2-mediated epigenetic control of RNA polymerase II (Pol II) transcribed coding gene transcription has been well established. However, little is known about EZH2-mediated epigenetic regulation of RNA polymerase III (Pol III) transcription. Here we present a paradigm that EZH2 is involved in the repression of Pol III transcription via interaction with transcriptio...
10 CitationsSource
#1Isabelle Thiffault (Children's Mercy Hospital)H-Index: 14
#2Nicole I. Wolf (VUmc: VU University Medical Center)H-Index: 50
Last. Geneviève Bernard (Montreal Children's Hospital)H-Index: 32
view all 27 authors...
A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodyst...
88 CitationsSource
#1Matt J. Silver (Lond: University of London)H-Index: 19
#2Noah J. Kessler (BCM: Baylor College of Medicine)H-Index: 8
Last. Robert A. Waterland (BCM: Baylor College of Medicine)H-Index: 41
view all 18 authors...
Background: Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants. Results: First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a g...
114 CitationsSource
#1Yong Sun Lee (UTMB: University of Texas Medical Branch)H-Index: 1
#1Yong Sun Lee (UTMB: University of Texas Medical Branch)H-Index: 19
nc886 (=vtRNA2-1, pre-miR-886, or CBL3) is a newly identified non-coding RNA (ncRNA) that represses the activity of protein kinase R (PKR). nc886 is transcribed by RNA polymerase III (Pol III) and is intriguingly the first case of a Pol III gene whose expression is silenced by CpG DNA hypermethylation in several types of cancer. PKR is a sensor protein that recognizes evading viruses and induces apoptosis to eliminate infected cells. Like viral infection, nc886 silencing activates PKR and induce...
29 CitationsSource
#1Damian GraczykH-Index: 9
#2Robert J. White (Ebor: University of York)H-Index: 54
Last. Kevin M. RyanH-Index: 60
view all 3 authors...
Inflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis, and metastasis. Enhanced cytokine production by TAMs is tightly coupled with protein synthesis. In turn, translation of proteins depends on tRNAs, short abundant transcripts that are made by RNA polymerase III (Pol III). Here, we connect these facts by showing t...
20 CitationsSource
Cited By17
Newest
#1Rafael Sebastián Fort (University of the Republic)H-Index: 6
#2María Ana Duhagon (University of the Republic)H-Index: 12
Background: The vault RNAs (vtRNAs) are a class of 84-141-nt eukaryotic non-coding RNAs transcribed by RNA polymerase III, associated to the ribonucleoprotein complex known as vault particle. Of the four human vtRNA genes, vtRNA1-1, vtRNA1-2 and vtRNA1-3, clustered at locus 1, are integral components of the vault particle, while vtRNA2-1 is a more divergent homologue located in a second locus. Gene expression studies of vtRNAs in large cohorts have been hindered by their unsuccessful sequencing ...
Source
#1Yeon-Su LeeH-Index: 24
#2Xiaoyong BaoH-Index: 23
Last. Yong Sun LeeH-Index: 3
view all 18 authors...
Interferons (IFNs) are a crucial component in the innate immune response. Especially the IFN-β signaling operates in most cell types and plays a key role in the first line of defense upon pathogen intrusion. The induction of IFN-β should be tightly controlled, because its hyperactivation can lead to tissue damage or autoimmune diseases. Activation of the IFN-β promoter needs Interferon Regulatory Factor 3 (IRF3), together with Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB...
Source
#1Rong‐hui Yang (Capital Medical University)H-Index: 3
#2Lingkun Zuo (Capital Medical University)H-Index: 1
Last. Lu Kong (Capital Medical University)H-Index: 3
view all 9 authors...
Abstract Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that nc886 is a representative Pol III gene that processes microRNA products via Dicer and further downregulates its target gene transforming growth factor- β1 (TGF-β1), which is the most prominent inducer of EMT in prostate cancer (PC). Consistent with the previous literature, we found that nc886 downregulation was strongly associated with metastatic behavior and ...
Source
#1Feixia Peng (WUST: Wuhan University of Science and Technology)H-Index: 2
#2Ying Zhou (WUST: Wuhan University of Science and Technology)H-Index: 4
Last. Wensheng Deng (WUST: Wuhan University of Science and Technology)H-Index: 6
view all 14 authors...
Specificity protein 1 (Sp1) is an important transcription factor implicated in numerous cellular processes. However, whether Sp1 is involved in the regulation of RNA polymerase (Pol )-directed gene transcription in human cells remains unknown. Here, we first show that filamin A (FLNA) represses Sp1 expression as well as expression of TFIIB-related factor 1 (BRF1) and general transcription factor C subunit 2(GTF3C2) in HeLa, 293T and SaOS2 cells lines stably expressing FLNA-silencing shRNAs. Both...
Source
#1Ji Yeon Han (SNU: Seoul National University)H-Index: 5
#1Ji Yeon Han (New Generation University College)H-Index: 1
Last. Jong Hee Chae (SNU: Seoul National University)H-Index: 28
view all 6 authors...
1 CitationsSource
#2Hannah BenistyH-Index: 5
Last. Luis Serrano (UPF: Pompeu Fabra University)H-Index: 118
view all 4 authors...
Different tissues express genes with particular codon usage and anticodon tRNA repertoires. However, the codon-anticodon co-adaptation in humans is not completely understood, nor is its effect on tissue-specific protein levels. Here, we first validated the accuracy of small RNA-seq for tRNA quantification across five human cell lines. We then analyzed the tRNA abundance of more than 8,000 tumor samples from TCGA, together with their paired mRNA-seq and proteomics data, to determine the Supply-to...
17 CitationsSource
#1Guillaume Hummel (UDS: University of Strasbourg)H-Index: 3
#2Jessica M. Warren (CSU: Colorado State University)H-Index: 8
Last. Laurence Drouard (UDS: University of Strasbourg)H-Index: 4
view all 3 authors...
: Transfer RNAs are among the most ancient molecules of life on earth. Beyond their crucial role in protein synthesis as carriers of amino acids, they are also important players in a plethora of other biological processes. Many debates in term of biogenesis, regulation and function persist around these fascinating non-coding RNAs. Our review focuses on the first step of their biogenesis in eukaryotes, i.e. their transcription from nuclear genes. Numerous and complementary ways have emerged durin...
13 CitationsSource
DNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells, suggesting that there are other cytotoxic mechanisms to be uncovered. By employing doxorubicin as a representative DNA-reactive compound, we have disc...
7 CitationsSource
#1Rochelle W Lai (SC: University of Southern California)H-Index: 3
#2Ryan Lu (SC: University of Southern California)H-Index: 3
Last. Bérénice A. Benayoun (SC: University of Southern California)H-Index: 27
view all 7 authors...
: In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity ...
24 CitationsSource
#1Ji Hye Ahn (Kyung Hee University)H-Index: 1
#2Hyun-Sung Lee (BCM: Baylor College of Medicine)H-Index: 25
Last. Yong Sun Lee (UTMB: University of Texas Medical Branch)H-Index: 19
view all 16 authors...
Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified n...
24 CitationsSource