scholarly journals Post-Transcriptional Regulation of Viral RNA through Epitranscriptional Modification

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1129
Author(s):  
David G. Courtney

The field of mRNA modifications has been steadily growing in recent years as technologies have improved and the importance of these residues became clear. However, a subfield has also arisen, specifically focused on how these modifications affect viral RNA, with the possibility that viruses can also be used as a model to best determine the role that these modifications play on cellular mRNAs. First, virologists focused on the most abundant internal mRNA modification, m6A, mapping this modification and elucidating its effects on the RNA of a wide range of RNA and DNA viruses. Next, less common RNA modifications including m5C, Nm and ac4C were investigated and also found to be present on viral RNA. It now appears that viral RNA is littered with a multitude of RNA modifications. In biological systems that are under constant evolutionary pressure to out compete both the host as well as newly arising viral mutants, it poses an interesting question about what evolutionary benefit these modifications provide as it seems evident, at least to this author, that these modifications have been selected for. In this review, I discuss how RNA modifications are identified on viral RNA and the roles that have now been uncovered for these modifications in regard to viral replication. Finally, I propose some interesting avenues of research that may shed further light on the exact role that these modifications play in viral replication.

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1049
Author(s):  
Belinda Baquero-Perez ◽  
Daryl Geers ◽  
Juana Díez

There are over 100 different chemical RNA modifications, collectively known as the epitranscriptome. N6-methyladenosine (m6A) is the most commonly found internal RNA modification in cellular mRNAs where it plays important roles in the regulation of the mRNA structure, stability, translation and nuclear export. This modification is also found in viral RNA genomes and in viral mRNAs derived from both RNA and DNA viruses. A growing body of evidence indicates that m6A modifications play important roles in regulating viral replication by interacting with the cellular m6A machinery. In this review, we will exhaustively detail the current knowledge on m6A modification, with an emphasis on its function in virus biology.


Author(s):  
Xiang Yu ◽  
Bishwas Sharma ◽  
Brian D Gregory

Abstract Ribonucleotides within the various RNA molecules in eukaryotes are marked with more than 160 distinct covalent chemical modifications. These modifications include those that occur internally in messenger RNA (mRNA) molecules such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), as well as those that occur at the ends of the modified RNAs like the non-canonical 5′ end nicotinamide adenine dinucleotide (NAD+) cap modification of specific mRNAs. Recent findings have revealed that covalent RNA modifications can impact the secondary structure, translatability, functionality, stability and degradation of the RNA molecules in which they are included. Many of these covalent RNA additions have also been found to be dynamically added and removed through writer and eraser complexes, respectively, providing a new layer of epitranscriptome-mediated post-transcriptional regulation that regulates RNA quality and quantity in eukaryotic transcriptomes. Thus, it is not surprising that the regulation of RNA fate mediated by these epitranscriptomic marks has been demonstrated to have widespread effects on plant development and the responses of these organisms to abiotic and biotic stresses. In this review, we highlight recent progress focused on the study of the dynamic nature of these epitranscriptome marks and their roles in post-transcriptional regulation during plant development and response to environmental cues, with an emphasis on the mRNA modifications of non-canonical 5′ end NAD+ capping, m6A and several other internal RNA modifications.


2010 ◽  
Vol 426 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Richard W. P. Smith ◽  
Nicola K. Gray

Cytoplasmic PABP [poly(A)-binding protein] is a multifunctional protein with well-studied roles in mRNA translation and stability. In the present review, we examine recent evidence that the activity of PABP is altered during infection with a wide range of viruses, bringing about changes in its stability, complex formation and intracellular localization. Targeting of PABP by both RNA and DNA viruses highlights the role of PABP as a central regulator of gene expression.


Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 436 ◽  
Author(s):  
Kavitha Ganesan Nathan ◽  
Sunil K. Lal

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.


2015 ◽  
Vol 43 (3) ◽  
pp. 323-327 ◽  
Author(s):  
Swagat Ray ◽  
Pól Ó Catnaigh ◽  
Emma C. Anderson

Unr (upstream of N-ras) is a eukaryotic RNA-binding protein that has a number of roles in the post-transcriptional regulation of gene expression. Originally identified as an activator of internal initiation of picornavirus translation, it has since been shown to act as an activator and inhibitor of cellular translation and as a positive and negative regulator of mRNA stability, regulating cellular processes such as mitosis and apoptosis. The different post-transcriptional functions of Unr depend on the identity of its mRNA and protein partners and can vary with cell type and changing cellular conditions. Recent high-throughput analyses of RNA–protein interactions indicate that Unr binds to a large subset of cellular mRNAs, suggesting that Unr may play a wider role in translational responses to cellular signals than previously thought.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 197
Author(s):  
Georg Wolff ◽  
Montserrat Bárcena

During infection with positive-strand RNA viruses, viral RNA synthesis associates with modified intracellular membranes that form unique and captivating structures in the cytoplasm of the infected cell. These viral replication organelles (ROs) play a key role in the replicative cycle of important human pathogens like coronaviruses, enteroviruses, or flaviviruses. From their discovery to date, progress in our understanding of viral ROs has closely followed new developments in electron microscopy (EM). This review gives a chronological account of this progress and an introduction to the different EM techniques that enabled it. With an ample repertoire of imaging modalities, EM is nowadays a versatile technique that provides structural and functional information at a wide range of scales. Together with well-established approaches like electron tomography or labeling methods, we examine more recent developments, such as volume scanning electron microscopy (SEM) and in situ cryotomography, which are only beginning to be applied to the study of viral ROs. We also highlight the first cryotomography analyses of viral ROs, which have led to the discovery of macromolecular complexes that may serve as RO channels that control the export of newly-made viral RNA. These studies are key first steps towards elucidating the macromolecular complexity of viral ROs.


Author(s):  
Brandon M. Sy ◽  
Jai J. Tree

Enteric and extraintestinal pathotypes of Escherichia coli utilize a wide range of virulence factors to colonize niches within the human body. During infection, virulence factors such as adhesins, secretions systems, or toxins require precise regulation and coordination to ensure appropriate expression. Additionally, the bacteria navigate rapidly changing environments with fluctuations in pH, temperature, and nutrient levels. Enteric pathogens utilize sophisticated, interleaved systems of transcriptional and post-transcriptional regulation to sense and respond to these changes and modulate virulence gene expression. Regulatory small RNAs and RNA-binding proteins play critical roles in the post-transcriptional regulation of virulence. In this review we discuss how the mosaic genomes of Escherichia coli pathotypes utilize small RNA regulation to adapt to their niche and become successful human pathogens.


2010 ◽  
Vol 38 (6) ◽  
pp. 1608-1614 ◽  
Author(s):  
Benoît Laloo ◽  
Marion Maurel ◽  
Sandra Jalvy-Delvaille ◽  
Francis Sagliocco ◽  
Christophe F. Grosset

An increasing number of arguments, including altered microRNA expression, support the idea that post-transcriptional deregulation participates in gene disturbances found in diseased tissues. To evaluate this hypothesis, we developed a method which facilitates post-transcriptional investigations in a wide range of human cells and experimental conditions. This method, called FunREG (functional, integrated and quantitative method to measure post-transcriptional regulation), connects lentiviral transduction with a fluorescent reporter system and quantitative PCR. Using FunREG, we efficiently measured post-transcriptional regulation mediated either by selected RNA sequences or regulatory factors (microRNAs), and then evaluated the contribution of mRNA decay and translation efficiency in the observed regulation. We demonstrated the existence of gene-specific post-transcriptional deregulation in liver tumour cells, and also reported a molecular link between a transcript variant abrogating HDAC6 (histone deacetylase 6) regulation by miR-433 and a rare familial genetic disease. Because FunREG is sensitive, quantitative and easy to use, many applications can be envisioned in fundamental and pathophysiological research.


Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1121
Author(s):  
Nikolay Manavski ◽  
Alexandre Vicente ◽  
Wei Chi ◽  
Jörg Meurer

Modifications in nucleic acids are present in all three domains of life. More than 170 distinct chemical modifications have been reported in cellular RNAs to date. Collectively termed as epitranscriptome, these RNA modifications are often dynamic and involve distinct regulatory proteins that install, remove, and interpret these marks in a site-specific manner. Covalent nucleotide modifications-such as methylations at diverse positions in the bases, polyuridylation, and pseudouridylation and many others impact various events in the lifecycle of an RNA such as folding, localization, processing, stability, ribosome assembly, and translational processes and are thus crucial regulators of the RNA metabolism. In plants, the nuclear/cytoplasmic epitranscriptome plays important roles in a wide range of biological processes, such as organ development, viral infection, and physiological means. Notably, recent transcriptome-wide analyses have also revealed novel dynamic modifications not only in plant nuclear/cytoplasmic RNAs related to photosynthesis but especially in chloroplast mRNAs, suggesting important and hitherto undefined regulatory steps in plastid functions and gene expression. Here we report on the latest findings of known plastid RNA modifications and highlight their relevance for the post-transcriptional regulation of chloroplast gene expression and their role in controlling plant development, stress reactions, and acclimation processes.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 43-OR
Author(s):  
DINA MOSTAFA ◽  
AKINORI TAKAHASHI ◽  
TADASHI YAMAMOTO

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