scholarly journals What are natural antisense transcripts good for?

2010 ◽  
Vol 38 (4) ◽  
pp. 1144-1149 ◽  
Author(s):  
Andreas Werner ◽  
Daniel Swan

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.

2013 ◽  
Vol 54 ◽  
pp. 79-90 ◽  
Author(s):  
Saba Valadkhan ◽  
Lalith S. Gunawardane

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.


2006 ◽  
Vol 2006 ◽  
pp. 1-13 ◽  
Author(s):  
Letizia Venturini ◽  
Matthias Eder ◽  
Michaela Scherr

In the past few years, the discovery of RNA-mediated gene silencing mechanisms, like RNA interference (RNAi), has revolutionized our understanding of eukaryotic gene expression. These mechanisms are activated by double-stranded RNA (dsRNA) and mediate gene silencing either by inducing the sequence-specific degradation of complementary mRNA or by inhibiting mRNA translation. RNAi now provides a powerful experimental tool to elucidate gene function in vitro and in vivo, thereby opening new exciting perspectives in the fields of molecular analysis and eventually therapy of several diseases such as infections and cancer. In hematology, numerous studies have described the successful application of RNAi to better define the role of oncogenic fusion proteins in leukemogenesis and to explore therapeutic approaches in hematological malignancies. In this review, we highlight recent advances and caveats relating to the application of this powerful new methodology to hematopoiesis.


2017 ◽  
Author(s):  
Tim Weenink ◽  
Robert M. McKiernan ◽  
Tom Ellis

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.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 93
Author(s):  
Peng Qin ◽  
Ann E. Loraine ◽  
Sheila McCormick

Background: cis-NATs (cis-natural antisense transcripts) are transcribed from opposite strands of adjacent genes and have been shown to regulate gene expression by generating small RNAs from the overlapping region. cis-NATs are important for plant development and resistance to pathogens and stress. Several genome-wide investigations identified a number of cis-NAT pairs, but these investigations predicted cis-NATS using expression data from bulk samples that included lots of cell types. Some cis-NAT pairs identified from those investigations might not be functional, because both transcripts of cis-NAT pairs need to be co-expressed in the same cell. Pollen only contains two cell types, two sperm and one vegetative cell, which makes cell-specific investigation of cis-NATs possible. Methods: We investigated potential protein-coding cis-NATs in pollen and sperm using pollen RNA-seq data and TAIR10 gene models using the Integrated Genome Browser.  We then used sperm microarray data and sRNAs in sperm and pollen to determine possibly functional cis-NATs in the sperm or vegetative cell, respectively. Results: We identified 1471 potential protein-coding cis-NAT pairs, including 131 novel pairs that were not present in TAIR10 gene models. In pollen, 872 possibly functional pairs were identified. 72 and 56 pairs were potentially functional in sperm and vegetative cells, respectively. sRNAs were detected at 794 genes, belonging to 739 pairs. Conclusion: These potential candidates in sperm and the vegetative cell are tools for understanding gene expression mechanisms in pollen.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Damien Mornico ◽  
Chung-Chau Hon ◽  
Mikael Koutero ◽  
Christian Weber ◽  
Jean-Yves Coppee ◽  
...  

AbstractNatural antisense transcripts (NAT) have been reported in prokaryotes and eukaryotes. While the functions of most reported NATs remain unknown, their potentials in regulating the transcription of their counterparts have been speculated. Entamoeba histolytica, which is a unicellular eukaryotic parasite, has a compact protein-coding genome with very short intronic and intergenic regions. The regulatory mechanisms of gene expression in this compact genome are under-described. In this study, by genome-wide mapping of RNA-Seq data in the genome of E. histolytica, we show that a substantial fraction of its protein-coding genes (28%) has significant transcription on their opposite strand (i.e. NAT). Intriguingly, we found the location of transcription start sites or polyadenylation sites of NAT are determined by the specific motifs encoded on the opposite strand of the gene coding sequences, thereby providing a compact regulatory system for gene transcription. Moreover, we demonstrated that NATs are globally up-regulated under various environmental conditions including temperature stress and pathogenicity. While NATs do not appear to be consequences of spurious transcription, they may play a role in regulating gene expression in E. histolytica, a hypothesis which needs to be tested.


Reproduction ◽  
2001 ◽  
pp. 41-48 ◽  
Author(s):  
CM Rodriguez ◽  
JL Kirby ◽  
BT Hinton

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.


Open Biology ◽  
2016 ◽  
Vol 6 (10) ◽  
pp. 160222 ◽  
Author(s):  
Grisel Cruz-Becerra ◽  
Mandy Juárez ◽  
Viviana Valadez-Graham ◽  
Mario Zurita

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.


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

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yajie Li ◽  
Xiaorong Li ◽  
Jun Yang ◽  
Yuke He

Abstract MicroRNAs (miRNAs) and natural antisense transcripts (NATs) control many biological processes and have been broadly applied for genetic manipulation of eukaryotic gene expression. Still unclear, however, are whether and how NATs regulate miRNA production. Here, we report that the cis-NATs of MIR398 genes repress the processing of their pri-miRNAs. Through genome-wide analysis of RNA sequencing data, we identify cis-NATs of MIRNA genes in Arabidopsis and Brassica. In Arabidopsis, MIR398b and MIR398c are coexpressed in vascular tissues with their antisense genes NAT398b and NAT398c, respectively. Knock down of NAT398b and NAT398c promotes miR398 processing, resulting in stronger plant thermotolerance owing to silencing of miR398-targeted genes; in contrast, their overexpression activates NAT398b and NAT398c, causing poorer thermotolerance due to the upregulation of miR398-targeted genes. Unexpectedly, overexpression of MIR398b and MIR398c activates NAT398b and NAT398c. Taken together, these results suggest that NAT398b/c repress miR398 biogenesis and attenuate plant thermotolerance via a regulatory loop.


2013 ◽  
Vol 47 (6) ◽  
pp. 796-802 ◽  
Author(s):  
D. Ya. Gurskiy ◽  
E. N. Nabirochkina ◽  
D. V. Kopytova

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