scholarly journals Modulated termination of non-coding transcription partakes in the regulation of gene expression

2021 ◽  
Author(s):  
Nouhou Haidara ◽  
Odil Porrua
Keyword(s):  
Catalytic Domain ◽  
Transcription Termination ◽  
Regulation Of Gene Expression ◽  
Gene Encoding ◽  
Genome Expression ◽  
Zn Homeostasis ◽  
Regulatory Capacity ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Pervasive Transcription

Pervasive transcription is a universal phenomenon leading to the production of a plethora of non-coding RNAs. If left uncontrolled, pervasive transcription can be harmful for genome expression and stability. However, non-coding transcription can also play important regulatory roles, for instance by promoting the repression of specific genes by a mechanism of transcriptional interference. The efficiency of transcription termination can strongly influence the regulatory capacity of non-coding transcription events, yet very little is known about the mechanisms modulating the termination of non-coding transcription in response to environmental cues. Here, we address this question by investigating the mechanisms that regulate the activity of the main actor in termination of non-coding transcription in budding yeast, the helicase Sen1. We identify a phosphorylation at a conserved threonine of the catalytic domain of Sen1 and we provide evidence that phosphorylation at this site reduces the efficiency of Sen1-mediated termination. Interestingly, we find that this phosphorylation impairs termination at an unannotated non-coding gene, thus repressing the expression of a downstream gene encoding the master regulator of Zn homeostasis, Zap1. Consequently, many additional genes exhibit an expression pattern mimicking conditions of Zn excess, where ZAP1 is naturally repressed. Our findings provide a novel paradigm of gene regulatory mechanism relying on the direct modulation of non-coding transcription termination.

The Role of microRNAs in the Viral Infections

2019 ◽  
Vol 24 (39) ◽  
pp. 4659-4667 ◽  
Author(s):  
Mona Fani ◽  
Milad Zandi ◽  
Majid Rezayi ◽  
Nastaran Khodadad ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Rna Viruses ◽  
Regulation Of Gene Expression ◽  
Molecular Structures ◽  
Main Function ◽  
Cellular Functions ◽  
Viral Genes ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

scholarly journals Direct Interactions with Nascent Transcripts Is Potentially a Common Targeting Mechanism of Long Non-Coding RNAs

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1483
Author(s):  
Ivan Antonov ◽  
Yulia Medvedeva
Keyword(s):  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Pilot Project ◽  
Base Pairing ◽  
Nascent Transcript ◽  
Active Transcription ◽  
Wet Lab ◽  
In Trans ◽  
Non Coding Rnas ◽  
Nascent Transcripts

Although thousands of mammalian long non-coding RNAs (lncRNAs) have been reported in the last decade, their functional annotation remains limited. A wet-lab approach to detect functions of a novel lncRNA usually includes its knockdown followed by RNA sequencing and identification of the deferentially expressed genes. However, identification of the molecular mechanism(s) used by the lncRNA to regulate its targets frequently becomes a challenge. Previously, we developed the ASSA algorithm that detects statistically significant inter-molecular RNA-RNA interactions. Here we designed a workflow that uses ASSA predictions to estimate the ability of an lncRNA to function via direct base pairing with the target transcripts (co- or post-transcriptionally). The workflow was applied to 300+ lncRNA knockdown experiments from the FANTOM6 pilot project producing statistically significant predictions for 71 unique lncRNAs (104 knockdowns). Surprisingly, the majority of these lncRNAs were likely to function co-transcriptionally, i.e., hybridize with the nascent transcripts of the target genes. Moreover, a number of the obtained predictions were supported by independent iMARGI experimental data on co-localization of lncRNA and chromatin. We detected an evolutionarily conserved lncRNA CHASERR (AC013394.2 or LINC01578) that could regulate target genes co-transcriptionally via interaction with a nascent transcript by directing CHD2 helicase. The obtained results suggested that this nuclear lncRNA may be able to activate expression of the target genes in trans by base-pairing with the nascent transcripts and directing the CHD2 helicase to the regulated promoters leading to open the chromatin and active transcription. Our study highlights the possible importance of base-pairing between nuclear lncRNAs and nascent transcripts for the regulation of gene expression.

scholarly journals Epigenetic roles of PIWI proteins and piRNAs in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Sadoughi ◽  
Seyyed Mehdi Mirhashemi ◽  
Zatollah Asemi
Keyword(s):  
Colorectal Cancer ◽  
Human Diseases ◽  
Regulatory Function ◽  
Epigenetic Alterations ◽  
Gastrointestinal Malignancy ◽  
Abnormal Expression ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Entire World

AbstractSmall non‐coding RNAs (sncRNAs) are a subgroup of non‐coding RNAs, with less than 200 nucleotides length and no potential for coding proteins. PiRNAs, a member of sncRNAs, were first discovered more than a decade ago and have attracted researcher’s attention because of their gene regulatory function both in the nucleus and in the cytoplasm. Recent investigations have found that the abnormal expression of these sncRNAs is involved in many human diseases, including cancers. Colorectal cancer (CRC), as a common gastrointestinal malignancy, is one of the important causes of cancer‐related deaths through the entire world and appears to be a consequence of mutation in the genome and epigenetic alterations. The aim of this review is to realize whether there is a relationship between CRC and piRNAs or not.

scholarly journals EVOLUTION AND VARIATION OF RENIN GENES IN MICE

Genetics ◽  
1984 ◽  
Vol 108 (3) ◽  
pp. 651-667
Author(s):  
Douglas P Dickinson ◽  
Kenneth W Gross ◽  
Nina Piccini ◽  
Carol M Wilson
Keyword(s):  
Gene Expression ◽  
Submandibular Gland ◽  
Regulation Of Gene Expression ◽  
Inbred Strains ◽  
Duplication Event ◽  
Comparative Sequence Analysis ◽  
Chromosome 1 ◽  
Gene Encoding ◽  
Prior Estimate ◽  
Low Levels

ABSTRACT Inbred strains of mice carry Ren-1, a gene encoding the thermostable Renin-1 isozyme. Ren-1 is expressed at relatively low levels in mouse submandibular gland and kidney. Some strains also carry Ren-2, a gene encoding the thermolabile Renin-2 isozyme. Ren-2 is expressed at high levels in the mouse submandibular gland and at very low levels, if at all, in the kidney. Ren-1 and Ren-2 are closely linked on mouse chromosome 1, show extensive homology in coding and noncoding regions and provide a model for studying the regulation of gene expression. An investigation of renin genes and enzymatic activity in wild-derived mice identified several restriction site polymorphisms as well as putative variants in renin gene expression and protein structure. The number of renin genes carried by different subpopulations of wild-derived mice is consistent with the occurrence of a gene duplication event prior to the divergence of M. spretus (2.75-5.5 million yr ago). This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice.

scholarly journals Non-Coding, RNAPII-Dependent Transcription at the Promoters of rRNA Genes Regulates Their Chromatin State in S. cerevisiae

2021 ◽  
Vol 7 (3) ◽  
pp. 41
Author(s):  
Emma Lesage ◽  
Jorge Perez-Fernandez ◽  
Sophie Queille ◽  
Christophe Dez ◽  
Olivier Gadal ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Tandem Repeats ◽  
Chromatin State ◽  
Rrna Genes ◽  
Rdna Genes ◽  
Regulatory Pathways ◽  
Chromatin States ◽  
Non Coding Rnas ◽  
Pervasive Transcription

Pervasive transcription is widespread in eukaryotes, generating large families of non-coding RNAs. Such pervasive transcription is a key player in the regulatory pathways controlling chromatin state and gene expression. Here, we describe long non-coding RNAs generated from the ribosomal RNA gene promoter called UPStream-initiating transcripts (UPS). In yeast, rDNA genes are organized in tandem repeats in at least two different chromatin states, either transcribed and largely depleted of nucleosomes (open) or assembled in regular arrays of nucleosomes (closed). The production of UPS transcripts by RNA Polymerase II from endogenous rDNA genes was initially documented in mutants defective for rRNA production by RNA polymerase I. We show here that UPS are produced in wild-type cells from closed rDNA genes but are hidden within the enormous production of rRNA. UPS levels are increased when rDNA chromatin states are modified at high temperatures or entering/leaving quiescence. We discuss their role in the regulation of rDNA chromatin states and rRNA production.

scholarly journals Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1132
Author(s):  
Emel Rothzerg ◽  
Xuan Dung Ho ◽  
Jiake Xu ◽  
David Wood ◽  
Aare Märtson ◽  
...  
Keyword(s):  
Tumour Progression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Osteosarcoma Cell ◽  
Osteoblast Cell Line ◽  
Antisense Lncrnas ◽  
Non Coding Rnas ◽  
Polymerase Chain ◽  
Multiple Levels

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.

scholarly journals Long non-coding RNAs in brain tumors

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Cancer ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diagnostic Biomarkers ◽  
Cancer Pathogenesis ◽  
Current State ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

scholarly journals Exosomic microRNAs as emerging key regulators of intercellular communication in the tumor microenvironment and beyond

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Mariam Murtadha ◽  
Muller Fabbri
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Intercellular Communication ◽  
Potential Role ◽  
Biological Fluids ◽  
Healthy Controls ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Regulatory Functions

AbstractMicroRNAs (miRs) are small non-coding RNAs with key gene regulatory functions. Recent evidence has shown that miRs have a central role in shaping the biology of the Tumor Microenvironment (TME). The discovery that some exosomes contain high levels of miR cargo that shuttle between cells and mediate intercellular cross-talk has shifted the focus of miR research towards understanding the biological role of exosomic miRs. In this review, we highlight the emerging role of exosomic miRs in molding the tumor microenvironment towards pro-tumor conditions by altering intercellular communication. We briefly discuss some mechanisms of selective loading of miRs into exosomes, as well as emerging evidence that exosomic miRs are present in all biological fluids. Furthermore, we describe the differences in the exosomic miR signatures between cancer patients and healthy controls, and the potential role of exosomic miRs as diagnostic, prognostic, and therapeutic biomarkers.

scholarly journals SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich's Ataxia

2019 ◽  
Vol 47 (20) ◽  
pp. 10728-10743 ◽  
Author(s):  
Carlotta Bon ◽  
Riccardo Luffarelli ◽  
Roberta Russo ◽  
Silvia Fortuni ◽  
Bianca Pierattini ◽  
...  
Keyword(s):  
Genetic Defect ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Monogenic Disease ◽  
Transcriptional Level ◽  
Gene Encoding ◽  
Mitochondrial Aconitase ◽  
Non Coding Rnas ◽  
Gaa Repeats

Abstract Friedreich's ataxia (FRDA) is an untreatable disorder with neuro- and cardio-degenerative progression. This monogenic disease is caused by the hyper-expansion of naturally occurring GAA repeats in the first intron of the FXN gene, encoding for frataxin, a protein implicated in the biogenesis of iron-sulfur clusters. As the genetic defect interferes with FXN transcription, FRDA patients express a normal frataxin protein but at insufficient levels. Thus, current therapeutic strategies are mostly aimed to restore physiological FXN expression. We have previously described SINEUPs, natural and synthetic antisense long non-coding RNAs, which promote translation of partially overlapping mRNAs through the activity of an embedded SINEB2 domain. Here, by in vitro screening, we have identified a number of SINEUPs targeting human FXN mRNA and capable to up-regulate frataxin protein to physiological amounts acting at the post-transcriptional level. Furthermore, FXN-specific SINEUPs promote the recovery of disease-associated mitochondrial aconitase defects in FRDA-derived cells. In summary, we provide evidence that SINEUPs may be the first gene-specific therapeutic approach to activate FXN translation in FRDA and, more broadly, a novel scalable platform to develop new RNA-based therapies for haploinsufficient diseases.

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