scholarly journals Abundances of transfer RNA modifications and transcriptional levels for tRNA-modifying enzymes are sex-specific in mosquitoes

2021 ◽  
Author(s):  
Melissa Kelley ◽  
Melissa R Uhran ◽  
Cassandra Herbert ◽  
George Yoshida ◽  
Emmarie Watts ◽  
...  
Keyword(s):  
Mosquito Species ◽  
Critical Factor ◽  
Transfer Rna ◽  
Trna Modification ◽  
Rna Modifications ◽  
Transcript Levels ◽  
Trna Modifications ◽  
Remediation Strategies ◽  
Adapter Molecule ◽  
Novel Target

As carriers of multiple human diseases, understanding the mechanisms behind mosquito reproduction may have implications for remediation strategies. Transfer RNA (tRNA) acts as the adapter molecule of amino acids and are key components in protein synthesis and a critical factor in the function of tRNAs is chemical modifications. Here, we provide an assessment of tRNA modifications between sexes for three mosquito species and examine correlated transcript levels underlying key proteins involved in tRNA modification. Thirty-three tRNA modifications were detected among mosquito species and most of these modifications are higher in females compared to males. Analysis of previous male and female RNAseq datasets indicated a similar increase in tRNA modifying enzymes in females, supporting our observed female enrichment of tRNA modifications. Tissues-specific expressional studies revealed high transcript levels for tRNA modifying enzymes in the ovaries for Aedes aegypti, but not male reproductive tissues. These studies suggest that tRNA modifications may be critical to reproduction in mosquitoes, representing a potential novel target for control.

Inflammatory Mechanisms in Parkinson’s Disease: From Pathogenesis to Targeted Therapies

2021 ◽  
pp. 107385842199226
Author(s):  
Stellina Y. H. Lee ◽  
Nathanael J. Yates ◽  
Susannah J. Tye
Keyword(s):  
Parkinson’S Disease ◽  
Central Nervous System ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Immune Cells ◽  
Critical Factor ◽  
Neurodegenerative Process ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Novel Target

Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson’s disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression. Biomarkers signifying the inflammatory and neurodegenerative processes at play within the central nervous system are of increasing interest to clinical teams. To be effective, such biomarkers must achieve the highest sensitivity and specificity for predicting PD risk, confirming diagnosis, or monitoring disease severity. The aim of this review was to summarize the current preclinical and clinical evidence that suggests that inflammatory processes contribute to the initiation and progression of neurodegenerative processes in PD. In this article, we further summarize the data about main inflammatory biomarkers described in PD to date and their potential for regulation as a novel target for disease-modifying pharmacological strategies.

scholarly journals A 2′-O-Methyltransferase Responsible for Transfer RNA Anticodon Modification Is Pivotal for Resistance to Pseudomonas syringae DC3000 in Arabidopsis

2018 ◽  
Vol 31 (12) ◽  
pp. 1323-1336 ◽  
Author(s):  
Vicente Ramírez ◽  
Beatriz González ◽  
Ana López ◽  
Maria Jose Castelló ◽  
Maria José Gil ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Pseudomonas Syringae ◽  
Bacterial Pathogen ◽  
Transfer Rna ◽  
Resistance Response ◽  
Chemical Structures ◽  
Trna Modifications ◽  
Trna Species ◽  
Living Organisms ◽  
And Function

Transfer RNA (tRNA) is the most highly modified class of RNA species in all living organisms. Recent discoveries have revealed unprecedented complexity in the tRNA chemical structures, modification patterns, regulation, and function, suggesting that each modified nucleoside in tRNA may have its own specific function. However, in plants, our knowledge of the role of individual tRNA modifications and how they are regulated is very limited. In a genetic screen designed to identify factors regulating disease resistance in Arabidopsis, we identified SUPPRESSOR OF CSB3 9 (SCS9). Our results reveal SCS9 encodes a tRNA methyltransferase that mediates the 2′-O-ribose methylation of selected tRNA species in the anticodon loop. These SCS9-mediated tRNA modifications enhance susceptibility during infection with the virulent bacterial pathogen Pseudomonas syringae DC3000. Lack of such tRNA modification, as observed in scs9 mutants, specifically dampens plant resistance against DC3000 without compromising the activation of the salicylic acid signaling pathway or the resistance to other biotrophic pathogens. Our results support a model that gives importance to the control of certain tRNA modifications for mounting an effective disease resistance in Arabidopsis toward DC3000 and, therefore, expands the repertoire of molecular components essential for an efficient disease resistance response.

scholarly journals Bacterial tRNA 2′-O-methylation is dynamically regulated under stress conditions and modulates innate immune response

2020 ◽  
Vol 48 (22) ◽  
pp. 12833-12844
Author(s):  
Adeline Galvanin ◽  
Lea-Marie Vogt ◽  
Antonia Grober ◽  
Isabel Freund ◽  
Lilia Ayadi ◽  
...  
Keyword(s):  
Gene Expression Regulation ◽  
Current Knowledge ◽  
Protein Translation ◽  
Stress Conditions ◽  
Transcriptional Level ◽  
Trna Modification ◽  
Rna Modifications ◽  
Swarming Motility ◽  
E Coli ◽  
Response To Stress

Abstract RNA modifications are a well-recognized way of gene expression regulation at the post-transcriptional level. Despite the importance of this level of regulation, current knowledge on modulation of tRNA modification status in response to stress conditions is far from being complete. While it is widely accepted that tRNA modifications are rather dynamic, such variations are mostly assessed in terms of total tRNA, with only a few instances where changes could be traced to single isoacceptor species. Using Escherichia coli as a model system, we explored stress-induced modulation of 2′-O-methylations in tRNAs by RiboMethSeq. This analysis and orthogonal analytical measurements by LC-MS show substantial, but not uniform, increase of the Gm18 level in selected tRNAs under mild bacteriostatic antibiotic stress, while other Nm modifications remain relatively constant. The absence of Gm18 modification in tRNAs leads to moderate alterations in E. coli mRNA transcriptome, but does not affect polysomal association of mRNAs. Interestingly, the subset of motility/chemiotaxis genes is significantly overexpressed in ΔTrmH mutant, this corroborates with increased swarming motility of the mutant strain. The stress-induced increase of tRNA Gm18 level, in turn, reduced immunostimulation properties of bacterial tRNAs, which is concordant with the previous observation that Gm18 is a suppressor of Toll-like receptor 7 (TLR7)-mediated interferon release. This documents an effect of stress induced modulation of tRNA modification that acts outside protein translation.

scholarly journals Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer

Genes ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 19 ◽  
Author(s):  
Harmen Hawer ◽  
Alexander Hammermeister ◽  
Keerthiraju Ravichandran ◽  
Sebastian Glatt ◽  
Raffael Schaffrath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Disease ◽  
Messenger Rna ◽  
Environmental Changes ◽  
Mrna Translation ◽  
Regulatory Control ◽  
Trna Modification ◽  
Positive Role ◽  
Trna Modifications

Transfer RNA (tRNA) is subject to a multitude of posttranscriptional modifications which can profoundly impact its functionality as the essential adaptor molecule in messenger RNA (mRNA) translation. Therefore, dynamic regulation of tRNA modification in response to environmental changes can tune the efficiency of gene expression in concert with the emerging epitranscriptomic mRNA regulators. Several of the tRNA modifications are required to prevent human diseases and are particularly important for proper development and generation of neurons. In addition to the positive role of different tRNA modifications in prevention of neurodegeneration, certain cancer types upregulate tRNA modification genes to sustain cancer cell gene expression and metastasis. Multiple associations of defects in genes encoding subunits of the tRNA modifier complex Elongator with human disease highlight the importance of proper anticodon wobble uridine modifications (xm5U34) for health. Elongator functionality requires communication with accessory proteins and dynamic phosphorylation, providing regulatory control of its function. Here, we summarized recent insights into molecular functions of the complex and the role of Elongator dependent tRNA modification in human disease.

scholarly journals Transfer RNA modifications and genes for modifying enzymes in Arabidopsis thaliana

2010 ◽  
Vol 10 (1) ◽  
pp. 201 ◽  
Author(s):  
Peng Chen ◽  
Gunilla Jäger ◽  
Bo Zheng
Keyword(s):  
Arabidopsis Thaliana ◽  
Transfer Rna ◽  
Rna Modifications

scholarly journals Regulatory roles of RNA modifications in breast cancer

NAR Cancer ◽  
2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Kanchan Kumari ◽  
Paula Groza ◽  
Francesca Aguilo
Keyword(s):  
Breast Cancer ◽  
Messenger Rna ◽  
Therapeutic Strategies ◽  
Rna Modifications ◽  
Breast Tumorigenesis ◽  
Cellular Processes ◽  
Trna Modifications ◽  
Expression Control ◽  
Gene Expression Control ◽  
Ribosomal Rrna

Abstract Collectively referred to as the epitranscriptome, RNA modifications play important roles in gene expression control regulating relevant cellular processes. In the last few decades, growing numbers of RNA modifications have been identified not only in abundant ribosomal (rRNA) and transfer RNA (tRNA) but also in messenger RNA (mRNA). In addition, many writers, erasers and readers that dynamically regulate the chemical marks have also been characterized. Correct deposition of RNA modifications is prerequisite for cellular homeostasis, and its alteration results in aberrant transcriptional programs that dictate human disease, including breast cancer, the most frequent female malignancy, and the leading cause of cancer-related death in women. In this review, we emphasize the major RNA modifications that are present in tRNA, rRNA and mRNA. We have categorized breast cancer-associated chemical marks and summarize their contribution to breast tumorigenesis. In addition, we describe less abundant tRNA modifications with related pathways implicated in breast cancer. Finally, we discuss current limitations and perspectives on epitranscriptomics for use in therapeutic strategies against breast and other cancers.

scholarly journals 7-Methylguanosine Modifications in Transfer RNA (tRNA)

2018 ◽  
Vol 19 (12) ◽  
pp. 4080 ◽  
Author(s):  
Chie Tomikawa
Keyword(s):  
Reaction Mechanism ◽  
Thermophilic Bacteria ◽  
Variable Region ◽  
Transfer Rna ◽  
Modified Nucleosides ◽  
Structural Studies ◽  
Trna Modifications ◽  
The Past ◽  
Methyl Transfer ◽  
Trna Structure

More than 90 different modified nucleosides have been identified in tRNA. Among the tRNA modifications, the 7-methylguanosine (m7G) modification is found widely in eubacteria, eukaryotes, and a few archaea. In most cases, the m7G modification occurs at position 46 in the variable region and is a product of tRNA (m7G46) methyltransferase. The m7G46 modification forms a tertiary base pair with C13-G22, and stabilizes the tRNA structure. A reaction mechanism for eubacterial tRNA m7G methyltransferase has been proposed based on the results of biochemical, bioinformatic, and structural studies. However, an experimentally determined mechanism of methyl-transfer remains to be ascertained. The physiological functions of m7G46 in tRNA have started to be determined over the past decade. For example, tRNA m7G46 or tRNA (m7G46) methyltransferase controls the amount of other tRNA modifications in thermophilic bacteria, contributes to the pathogenic infectivity, and is also associated with several diseases. In this review, information of tRNA m7G modifications and tRNA m7G methyltransferases is summarized and the differences in reaction mechanism between tRNA m7G methyltransferase and rRNA or mRNA m7G methylation enzyme are discussed.

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