scholarly journals Deciphering Epitranscriptome: Modification of mRNA Bases Provides a New Perspective for Post-transcriptional Regulation of Gene Expression

Author(s):  
Suresh Kumar ◽  
Trilochan Mohapatra

Gene regulation depends on dynamic and reversibly modifiable biological and chemical information in the epigenome/epitranscriptome. Accumulating evidence suggests that messenger RNAs (mRNAs) are generated in flashing bursts in the cells in a precisely regulated manner. However, the different aspects of the underlying mechanisms are not fully understood. Cellular RNAs are post-transcriptionally modified at the base level, which alters the metabolism of mRNA. The current understanding of epitranscriptome in the animal system is far ahead of that in plants. The accumulating evidence indicates that the epitranscriptomic changes play vital roles in developmental processes and stress responses. Besides being non-genetically encoded, they can be of reversible nature and involved in fine-tuning the expression of gene. However, different aspects of base modifications in mRNAs are far from adequate to assign the molecular basis/functions to the epitranscriptomic changes. Advances in the chemogenetic RNA-labeling and high-throughput next-generation sequencing techniques are enabling functional analysis of the epitranscriptomic modifications to reveal their roles in mRNA biology. Mapping of the common mRNA modifications, including N6-methyladenosine (m6A), and 5-methylcytidine (m5C), have enabled the identification of other types of modifications, such as N1-methyladenosine. Methylation of bases in a transcript dynamically regulates the processing, cellular export, translation, and stability of the mRNA; thereby influence the important biological and physiological processes. Here, we summarize the findings in the field of mRNA base modifications with special emphasis on m6A, m5C, and their roles in growth, development, and stress tolerance, which provide a new perspective for the regulation of gene expression through post-transcriptional modification. This review also addresses some of the scientific and technical issues in epitranscriptomic study, put forward the viewpoints to resolve the issues, and discusses the future perspectives of the research in this area.

2003 ◽  
Vol 195 (3) ◽  
pp. 356-372 ◽  
Author(s):  
Annamaria Bevilacqua ◽  
Maria Cristina Ceriani ◽  
Sergio Capaccioli ◽  
Angelo Nicolin

2020 ◽  
Author(s):  
Nadav Eisner ◽  
Tzofia Maymon ◽  
Ester Cancho Sanchez ◽  
Dana Bar-Zvi ◽  
Sagie Brodsky ◽  
...  

AbstractThe transcription factor ABA-INSENSITIVE(ABI)4 has diverse roles in regulating plant growth, including inhibiting germination and reserve mobilization in response to ABA and high salinity, inhibiting seedling growth in response to high sugars, inhibiting lateral root growth, and repressing light-induced gene expression. ABI4 activity is regulated at multiple levels, including gene expression, protein stability, and activation by phosphorylation. Although ABI4 can be phosphorylated at multiple residues by MAPKs, we found that S114 is the preferred site of MPK3. To examine the possible biological role of S114 phosphorylation, we transformed abi4-1 mutant plants with ABI4pro::ABI4 constructs encoding wild type (114S), phosphorylation-null (S114A) or phosphomimetic (S114E) forms of ABI4. Phosphorylation of S114 is necessary for the response to ABA, glucose, salt stress, and lateral root development, where the abi4 phenotype could be complemented by expressing ABI4(114S) or ABI4(S114E) but not ABI4(S114A). Comparison of root transcriptomes in ABA-treated roots of abi4-1 mutant plants transformed with constructs encoding the different phosphorylation-forms of S114 of ABI4 revealed that 85% of the ABI4-regulated genes whose expression pattern could be restored by expressing ABI4(114S) are down-regulated by ABI4. Over half of the ABI4-modulated genes were independent of the phosphorylation state of ABI4; these are enriched for stress responses. Phosphorylation of S114 was required for regulation of 35% of repressed genes, but only 17% of induced genes. The genes whose repression requires the phosphorylation of S114 are mainly involved in embryo and seedling development, growth and differentiation, and regulation of gene expression.HighlightsTranscription factor ABI4 is a substrate of MAP kinases.MPK3 preferentially phosphorylates Serine 114 of ABI4.Phosphorylated Serine 114 of ABI4 is required for the complementation of abi4 mutants.Phosphorylated ABI4 acts primarily as a repressor.


2021 ◽  
Author(s):  
Steven G. Fagan ◽  
Shona Pfeiffer

Advancements in RNA sequencing technologies in recent years have contributed greatly to our understanding of the transcriptome and the now widely recognized multifaceted functions of RNA. The discovery and functional analysis of an increasing number of novel small non-coding RNAs (ncRNAs) has highlighted their importance as critical regulators of gene expression and brain function. In particular, two diverse classes of ncRNAs, microRNAs (miRNAs) and tRNA-derived small RNAs (tsRNAs), are especially abundant in the nervous system and play roles in regulation of gene expression and protein translation, cellular stress responses and complex underlying pathophysiology of neurological diseases. This chapter will discuss the most recent findings highlighting the dysregulation, functions and regulatory roles of ncRNAs in the pathophysiological mechanisms of neurological disorders and their relevance as novel biomarkers of injury and therapeutic agents.


Author(s):  
Fanli Meng ◽  
Hainan Zhao ◽  
Bo Zhu ◽  
Tao Zhang ◽  
Mingyu Yang ◽  
...  

Abstract Enhancers located in introns are abundant and play a major role in the regulation of gene expression in mammalian species. By contrast, the functions of intronic enhancers in plants have largely been unexplored and only a handful of plant intronic enhancers have been reported. We performed a genome-wide prediction of intronic enhancers in Arabidopsis thaliana using open chromatin signatures based on DNase I sequencing. We identified 941 candidate intronic enhancers associated with 806 genes in seedling tissue and 1,271 intronic enhancers associated with 1,069 genes in floral tissue. We validated the function of 15 of 21 (71%) of the predicted intronic enhancers in transgenic assays using a reporter gene. We also created deletion lines of three intronic enhancers associated with two different genes using CRISPR/Cas. Deletion of these enhancers, which span key transcription factor binding sites, did not abolish gene expression but caused varying levels of transcriptional repression of their cognate genes. Remarkably, the transcriptional repression of the deletion lines occurred at specific developmental stages and resulted in distinct phenotypic effects on plant morphology and development. Clearly, these three intronic enhancers are important in fine-tuning tissue- and development-specific expression of their cognate genes.


2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Simone Balzer Le ◽  
Ingerid Onsager ◽  
Jon Andreas Lorentzen ◽  
Rahmi Lale

Abstract Bacterial 5′ untranslated regions of mRNA (UTR) involve in a complex regulation of gene expression; however, the exact sequence features contributing to gene regulation are not yet fully understood. In this study, we report the design of a novel 5′ UTR, dual UTR, utilizing the transcriptional and translational characteristics of 5′ UTRs in a single expression cassette. The dual UTR consists of two 5′ UTRs, each separately leading to either increase in transcription or translation of the reporter, that are separated by a spacer region, enabling de novo translation initiation. We rationally create dual UTRs with a wide range of expression profiles and demonstrate the functionality of the novel design concept in Escherichia coli and Pseudomonas putida using different promoter systems and coding sequences. Overall, we demonstrate the application potential of dual UTR design concept in various synthetic biology applications ranging from fine-tuning of gene expression to maximization of protein production.


2012 ◽  
Vol 79 (2) ◽  
pp. 707-713 ◽  
Author(s):  
Behnam Nazari ◽  
Michihiko Kobayashi ◽  
Akihiro Saito ◽  
Azam Hassaninasab ◽  
Kiyotaka Miyashita ◽  
...  

ABSTRACTMicroarray analyses revealed that the expression of genes for secondary metabolism together with that of primary metabolic genes was induced by chitin in autoclaved soil cultures ofStreptomyces coelicolorA3(2). The data also indicated that DasR was involved in the regulation of gene expression for chitin catabolism, secondary metabolism, and stress responses.


2012 ◽  
Vol 40 (10) ◽  
pp. 4368-4384 ◽  
Author(s):  
M. Carmen Ortells ◽  
Beatriz Morancho ◽  
Katherine Drews-Elger ◽  
Benoit Viollet ◽  
Keith R. Laderoute ◽  
...  

2020 ◽  
Author(s):  
Maria Cecília Zorél Meneghetti ◽  
Paula Deboni ◽  
Carlos Modesto Vera Palomino ◽  
Luiz Patekoski Braga ◽  
Renan Pelluzzi Cavalheiro ◽  
...  

AbstractThe cell surface and extracellular matrix polysaccharide, heparan sulfate (HS) conveys chemical information to control or influence crucial biological processes. Attempts to describe its structure-function relationships with HS binding proteins in a classical ‘lock and key’ type manner, however, have been unsuccessful. HS chains are synthesized in a non-template driven process in the ER and Golgi apparatus, involving a large number of enzymes capable of fine-tuning structures. Changes in the localization of HS-modifying enzymes throughout the Golgi, rather than protein expression levels, were found to correlate with changes in the structure of HS. Following brefeldin A treatment, the HS-modifying enzymes localized preferentially in COPII vesicles and at the trans-Golgi. Further, shortly after treatment with heparin, the HS-modifying enzyme moved from cis to trans-Golgi, which coincided with increased HS trisulfated disaccharide content. Finally, it was shown that COPI subunits and Sec24 gene expression changed. Collectively, these findings highlight that the ER-Golgi dynamics of HS-modifying enzymes via vesicular trafficking processes are critical prerequisite for the complete delineation of HS biosynthesis.


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