scholarly journals RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 627
Author(s):  
Amber Willbanks ◽  
Shaun Wood ◽  
Jason X. Cheng
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Fine Tuning ◽  
Human Diseases ◽  
Rna Modifications ◽  
Regulate Gene Expression ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Fine Tune

Chromatin structure plays an essential role in eukaryotic gene expression and cell identity. Traditionally, DNA and histone modifications have been the focus of chromatin regulation; however, recent molecular and imaging studies have revealed an intimate connection between RNA epigenetics and chromatin structure. Accumulating evidence suggests that RNA serves as the interplay between chromatin and the transcription and splicing machineries within the cell. Additionally, epigenetic modifications of nascent RNAs fine-tune these interactions to regulate gene expression at the co- and post-transcriptional levels in normal cell development and human diseases. This review will provide an overview of recent advances in the emerging field of RNA epigenetics, specifically the role of RNA modifications and RNA modifying proteins in chromatin remodeling, transcription activation and RNA processing, as well as translational implications in human diseases.

Role of small nuclear RNAs in eukaryotic gene expression

2013 ◽  
Vol 54 ◽  
pp. 79-90 ◽  
Author(s):  
Saba Valadkhan ◽  
Lalith S. Gunawardane
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Stability ◽  
Splice Sites ◽  
Branch Site ◽  
Small Nuclear Rnas ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

scholarly journals What are natural antisense transcripts good for?

2010 ◽  
Vol 38 (4) ◽  
pp. 1144-1149 ◽  
Author(s):  
Andreas Werner ◽  
Daniel Swan
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Higher Order ◽  
Transcriptional Gene Silencing ◽  
Antisense Transcripts ◽  
Natural Antisense Transcripts ◽  
Protein Coding ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene

NATs (natural antisense transcripts) are important regulators of eukaryotic gene expression. Interference between the expression of protein-coding sense transcripts and the corresponding NAT is well documented. In the present review, we focus on an additional, higher-order role of NATs that is currently emerging. The recent discovery of endogenous siRNAs (short interfering RNAs), as well as NAT-induced transcriptional gene silencing, are key to the proposed novel function of NATs.

scholarly journals Rational Design of RNA Structures that Predictably Tune Eukaryotic Gene Expression

2017 ◽  
Author(s):  
Tim Weenink ◽  
Robert M. McKiernan ◽  
Tom Ellis
Keyword(s):  
Gene Expression ◽  
Rational Design ◽  
Rna Structures ◽  
Genetic Circuits ◽  
Protein Coding ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Engineering Projects ◽  
Fine Tune ◽  
Different Levels

AbstractPredictable tuning of gene expression is essential for engineering genetic circuits and for optimising enzyme levels in metabolic engineering projects. In bacteria, gene expression can be tuned at the stage of transcription, by exchanging the promoter, or at stage of translation by altering the ribosome binding site sequence. In eukaryotes, however, only promoter exchange is regularly used, as the tools to modulate translation are lacking. Working in S. cerevisiae yeast, we here describe how hairpin RNA structures inserted into the 5’ untranslated region (5’UTR) of mRNAs can be used to tune expression levels by altering the efficiency of translation initiation. We demonstrate a direct link between the calculated free energy of folding in the 5’UTR and protein abundance, and show that this enables rational design of hairpin libraries that give predicted expression outputs. Our approach is modular, working with different promoters and protein coding sequences, and it outperforms promoter mutation as a way to predictably generate a library where a protein is induced to express at a range of different levels. With this tool, computational RNA sequence design can be used to predictably fine-tune protein production, providing a new way to modulate gene expression in eukaryotes.

scholarly journals Regulation of gene transcription in the epididymis

Reproduction ◽  
2001 ◽  
pp. 41-48 ◽  
Author(s):  
CM Rodriguez ◽  
JL Kirby ◽  
BT Hinton
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Potential Role ◽  
Transcriptional Level ◽  
Spatial And Temporal Patterns ◽  
Critical Control Points ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Dna Elements

The epididymis exhibits region-specific as well as cell-specific patterns of gene expression within the epithelium. The spatial and temporal patterns of gene expression originate during development and are critical to the formation and maintenance of a fully functional epididymis. Despite the number of mechanisms reported to contribute to the regulation of eukaryotic gene expression, little is known about the specific mechanisms involved in the control of epididymal gene expression. This review will outline some of the cis-DNA elements and associated transcription factors that have been identified in the epididymis, in addition to discussing the potential role of co-regulator molecules and changes in chromatin structure as critical control points of gene expression. Although gene expression can be controlled at several points, discussion will focus on gene regulation at the transcriptional level. The role of post-transcriptional control, with particular attention to mRNA stability, will also be discussed.

scholarly journals Analysis of Drosophila p8 and p52 mutants reveals distinct roles for the maintenance of TFIIH stability and male germ cell differentiation

Open Biology ◽  
2016 ◽  
Vol 6 (10) ◽  
pp. 160222 ◽  
Author(s):  
Grisel Cruz-Becerra ◽  
Mandy Juárez ◽  
Viviana Valadez-Graham ◽  
Mario Zurita
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Cell Differentiation ◽  
Germ Cell ◽  
Specific Cell ◽  
Germ Cell Differentiation ◽  
Specific Syndrome ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene

Eukaryotic gene expression is activated by factors that interact within complex machinery to initiate transcription. An important component of this machinery is the DNA repair/transcription factor TFIIH. Mutations in TFIIH result in three human syndromes: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Transcription and DNA repair defects have been linked to some clinical features of these syndromes. However, how mutations in TFIIH affect specific developmental programmes, allowing organisms to develop with particular phenotypes, is not well understood. Here, we show that mutations in the p52 and p8 subunits of TFIIH have a moderate effect on the gene expression programme in the Drosophila testis, causing germ cell differentiation arrest in meiosis, but no Polycomb enrichment at the promoter of the affected differentiation genes, supporting recent data that disagree with the current Polycomb-mediated repression model for regulating gene expression in the testis. Moreover, we found that TFIIH stability is not compromised in p8 subunit-depleted testes that show transcriptional defects, highlighting the role of p8 in transcription. Therefore, this study reveals how defects in TFIIH affect a specific cell differentiation programme and contributes to understanding the specific syndrome manifestations in TFIIH-afflicted patients.

scholarly journals The Role of the O-GlcNAc Modification in Regulating Eukaryotic Gene Expression

2010 ◽  
Vol 5 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Sandii Brimble ◽  
Edith Wollaston-Hayden ◽  
Chin Teo ◽  
Andrew Morris ◽  
Lance Wells
Keyword(s):  
Gene Expression ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene

scholarly journals Regulation of Gene Expression under Hypoxic Conditions

2019 ◽  
Vol 20 (13) ◽  
pp. 3278 ◽  
Author(s):  
Koh Nakayama ◽  
Naoyuki Kataoka
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Rna Splicing ◽  
Regulation Of Gene Expression ◽  
Splicing Factors ◽  
Rna Transport ◽  
Regulate Gene Expression ◽  
Hypoxic Conditions ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene

Eukaryotes are often subjected to different kinds of stress. In order to adjust to such circumstances, eukaryotes activate stress–response pathways and regulate gene expression. Eukaryotic gene expression consists of many different steps, including transcription, RNA processing, RNA transport, and translation. In this review article, we focus on both transcriptional and post-transcriptional regulations of gene expression under hypoxic conditions. In the first part of the review, transcriptional regulations mediated by various transcription factors including Hypoxia-Inducible Factors (HIFs) are described. In the second part, we present RNA splicing regulations under hypoxic conditions, which are mediated by splicing factors and their kinases. This work summarizes and discusses the emerging studies of those two gene expression machineries under hypoxic conditions.

Role of multifunctional coactivator complex SAGA in regulation of eukaryotic gene expression

2013 ◽  
Vol 47 (6) ◽  
pp. 796-802 ◽  
Author(s):  
D. Ya. Gurskiy ◽  
E. N. Nabirochkina ◽  
D. V. Kopytova
Keyword(s):  
Gene Expression ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Coactivator Complex

scholarly journals SPATIAL ORGANIZATION OF TRANSCRIBED EUKARYOTIC GENES

2020 ◽  
Author(s):  
Susanne Leidescher ◽  
Johannes Nübler ◽  
Yana Feodorova ◽  
Erica Hildebrand ◽  
Simon Ullrich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Organization ◽  
Regulation Of Gene Expression ◽  
Spatial Arrangement ◽  
Eukaryotic Genes ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Intrinsic Stiffness ◽  
Established Role

SUMMARYDespite the well established role of nuclear organization in the regulation of gene expression, little is known about the reverse: how transcription shapes the spatial organization of the genome. In particular, given the relatively small sizes of genes and the limited resolution of light microscopy, the structure and spatial arrangement of a single transcribed gene are still poorly understood. Here, we make use of several long highly expressed mammalian genes and demonstrate that they form Transcription Loops (TLs) with polymerases moving along the loops and carrying nascent RNAs that undergo co-transcriptional splicing. TLs dynamically modify their harboring loci and extend into the nuclear interior suggesting an intrinsic stiffness. Both experimental evidence and polymer modeling support the hypothesis that TL stiffness is caused by the dense decoration of transcribed genes with multiple voluminous nascent RNPs. We propose that TL formation is a universal principle of eukaryotic gene expression.

scholarly journals Epitranscriptomics: A New Layer of microRNA Regulation in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3372
Author(s):  
Veronica De Paolis ◽  
Elisa Lorefice ◽  
Elisa Orecchini ◽  
Claudia Carissimi ◽  
Ilaria Laudadio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Potential Role ◽  
Fine Tuning ◽  
Cancer Development ◽  
Transcriptional Level ◽  
Rna Modifications ◽  
Gene Expressions ◽  
Microrna Regulation ◽  
Non Coding Rnas

MicroRNAs are pervasive regulators of gene expression at the post-transcriptional level in metazoan, playing key roles in several physiological and pathological processes. Accordingly, these small non-coding RNAs are also involved in cancer development and progression. Furthermore, miRNAs represent valuable diagnostic and prognostic biomarkers in malignancies. In the last twenty years, the role of RNA modifications in fine-tuning gene expressions at several levels has been unraveled. All RNA species may undergo post-transcriptional modifications, collectively referred to as epitranscriptomic modifications, which, in many instances, affect RNA molecule properties. miRNAs are not an exception, in this respect, and they have been shown to undergo several post-transcriptional modifications. In this review, we will summarize the recent findings concerning miRNA epitranscriptomic modifications, focusing on their potential role in cancer development and progression.

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