Modified nucleotides in mRNA are an essential addition to the standard genetic code of four nucleotides in animals, plants, and their viruses. The emerging field of epitranscriptomics examines nucleotide modifications in mRNA and their impact on gene expression. The low abundance of nucleotide modifications and technical limitations, however, have hampered systematic analysis of their occurrence and functions. Selective chemical and immunological identification of modified nucleotides has revealed global candidate topology maps for many modifications in mRNA, but further technical advances to increase confidence will be necessary. Single-molecule sequencing introduced by Oxford Nanopore now promises to overcome such limitations, and we summarize current progress with a particular focus on the bioinformatic challenges of this novel sequencing technology. Epitranscriptomics -A Rapidly Developing FieldChemical modifications on RNA are well-established and evolutionarily conserved features of structural RNAs such as rRNA and tRNA [1-3]. In the past few years the occurrence of these modifications on protein-coding mRNAs, long noncoding RNAs (lncRNAs), and small regulatory RNAs (srRNAs) has received renewed attention to determine their role in regulating gene expression, development, and health and disease (Box 1). The rapid evolution of transcriptome sequencing technologies has made it possible to develop methodologies that interrogate the topography of RNA modifications transcriptome-wide. This new field, termed epitranscriptomics (see Glossary), seeks to elucidate the role of RNA modifications in regulating gene expression, with a special focus on their biological functions in mRNA.
Most of the analyses on the conservation of gene order are limited to orthologous genes. However, the organization of genes into operons might also result in the conservation of gene order of paralogous genes. Thus, we sought computational evidence that conservation of gene order of paralogous genes represents another level of conservation of genes in operons. We found that pairs of genes within experimentally characterized operons of Escherichia coli K12 and Bacillus subtilis tend to have more adjacently conserved paralogs than pairs of genes at transcription unit boundaries. The fraction of same strand gene pairs corresponding to conserved paralogs averages 0.07 with a maximum of 0.22 in Borrelia burgdorferi. The use of evidence from the conservation of adjacency of paralogous genes can improve the prediction of operons in E.coli K12 by approximately 0.27 over predictions using conservation of adjacency of orthologous genes alone.
Background: Bcl6 is required for the development of T follicular helper and regulatory (Tfh, Tfr) cells that regulate germinal center responses. Bcl6 also impacts the function of regulatory T (Treg) cells. Objective:The goal of this study is to define the functions of Bcl6 in Treg cells including Tfr cells in the context of allergic airway inflammation (AAI). Methods: We employed a model of house dust mite (HDM) sensitization to challenge wild type, Bcl6 fl/fl Foxp3-Cre and Prdm1(Blimp1) fl/fl Foxp3-Cre mice to study the reciprocal roles of Bcl6 and Blimp1 in AAI. Results: In the HDM model, Tfr cells repress the production of IgE and Bcl6+ Treg cells suppress the generation of type 2 cytokine producing cells in the lungs. In mice with Bcl6deficient Treg cells, twice as many ST2 (IL-33R) + Tregs develop as observed in wild type mice. ST2 + Tregs in the context of AAI are Blimp1-dependent, express type 2 cytokines, and share features of visceral adipose tissue Treg cells. Bcl6-deficient Tregs are more susceptible, and Blimp1-deficient Tregs are resistant, to acquiring the ST2 + Treg cell phenotype in vitro and in vivo in response to IL-33. Bcl6-deficient ST2+ Tregs but not Bcl6-deficient ST2+ T conventional cells strongly promote AAI when transferred into recipient mice. Lastly, ST2 is required for the exacerbated AAI in Bcl6 fl/fl Foxp3-Cre mice. Conclusions: During AAI, Bcl6 and Blimp1 play dual roles in regulating Tfr activity in the germinal center and in the development of ST2 + Tregs that promote type 2 cytokine responses. Koh page 4 4 Key Messages: • Tfr cells limit IgE production in mice challenged by airway allergen • Bcl6 and Blimp1 reciprocally regulate ST2 + Treg development • ST2 + Tregs promote allergic airway inflammation Capsule Summary: Bcl6 attenuates allergic disease by promoting Tfr cell development to repress the allergen-specific humoral response and by limiting expansion of ST2 + Tregs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.