Dynamics of transcriptional and post-transcriptional regulation

Abstract Despite gene expression programs being notoriously complex, RNA abundance is usually assumed as a proxy for transcriptional activity. Recently developed approaches, able to disentangle transcriptional and post-transcriptional regulatory processes, have revealed a more complex scenario. It is now possible to work out how synthesis, processing and degradation kinetic rates collectively determine the abundance of each gene’s RNA. It has become clear that the same transcriptional output can correspond to different combinations of the kinetic rates. This underscores the fact that markedly different modes of gene expression regulation exist, each with profound effects on a gene’s ability to modulate its own expression. This review describes the development of the experimental and computational approaches, including RNA metabolic labeling and mathematical modeling, that have been disclosing the mechanisms underlying complex transcriptional programs. Current limitations and future perspectives in the field are also discussed.

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A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqz006 ◽

2019 ◽

Vol 2 (1) ◽

Author(s):

Nelly F Mostajo ◽

Marie Lataretu ◽

Sebastian Krautwurst ◽

Florian Mock ◽

Daniel Desirò ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Large Scale ◽

Viral Infections ◽

Gene Expression Regulation ◽

Expression Patterns ◽

Differential Expression Analysis ◽

Regulatory Processes ◽

Genome Annotations ◽

Host Virus Interactions

Abstract Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.

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RNA Modifications in the Central Nervous System

The Oxford Handbook of Neuronal Protein Synthesis ◽

10.1093/oxfordhb/9780190686307.013.23 ◽

2020 ◽

Cited By ~ 1

Author(s):

Dan Ohtan Wang

Keyword(s):

Gene Expression ◽

Cell Function ◽

Gene Expression Regulation ◽

Spinal Injury ◽

Regulation Of Gene Expression ◽

Modified Nucleosides ◽

Rna Modifications ◽

The Central Nervous System ◽

Post Transcriptional Regulation ◽

The Brain

Epitranscriptomics, a recently emerged field to investigate post-transcriptional regulation of gene expression through enzyme-mediated RNA modifications, is rapidly evolving and integrating with neuroscience. Using a rich repertoire of modified nucleosides and strategically positioning them to the functionally important and evolutionarily conserved regions of the RNA, epitranscriptomics dictates RNA-mediated cell function. The new field is quickly changing our view of the genetic geography in the brain during development and plasticity, impacting major functions from cortical neurogenesis, circadian rhythm, learning and memory, to reward, addiction, stress, stroke, and spinal injury, etc. Thus understanding the molecular components and operational rules of this pathway is becoming a key for us to decipher the genetic code for brain development, function, and disease. What RNA modifications are expressed in the brain? What RNAs carry them and rely on them for function? Are they dynamically regulated? How are they regulated and how do they contribute to gene expression regulation and brain function? This chapter summarizes recent advances that are beginning to answer these questions.

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Genome-wide dynamics of RNA synthesis, processing and degradation without RNA metabolic labeling

10.1101/520155 ◽

2019 ◽

Cited By ~ 3

Author(s):

Mattia Furlan ◽

Eugenia Galeota ◽

Nunzio Del Gaudio ◽

Erik Dassi ◽

Michele Caselle ◽

...

Keyword(s):

Transcriptional Regulation ◽

Steady State ◽

Time Course ◽

Rna Synthesis ◽

Computational Method ◽

Metabolic Labeling ◽

Experimental Conditions ◽

Rna Dynamics ◽

Kinetic Rates ◽

Post Transcriptional Regulation

AbstractThe kinetic rates of RNA synthesis, processing and degradation determine the dynamics of transcriptional regulation by governing both the abundance and the responsiveness to modulations of premature and mature RNA species. The study of RNA dynamics is largely based on the integrative analysis of total and nascent transcription, with the latter being quantified through RNA metabolic labeling. We describe here INSPEcT-, a computational method based on mathematical modeling of intronic and exonic expression, able to derive the dynamics of transcription from steady state or time course profiling of just total RNA, without requiring any information on nascent transcripts. Our approach closely recapitulates the kinetic rates obtained through RNA metabolic labeling, improves the ability to detect changes in transcripts half-lives, reduces the cost and complexity of the experiments, and can be adopted to study experimental conditions where nascent transcription cannot be readily profiled. Finally, we applied INSPEcT- to the characterization of post-transcriptional regulation landscapes in dozens of physiological and disease conditions. This approach was included in the INSPEcT Bioconductor package, which can now unveil RNA dynamics from steady state or time course data, with or without the profiling of nascent RNA.

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Enhanced Transcriptome Maps from Multiple Mouse Tissues Reveal Evolutionary Constraint in Gene Expression for Thousands of Genes

10.1101/010884 ◽

2014 ◽

Cited By ~ 1

Author(s):

Dmitri Pervouchine ◽

Sarah Djebali ◽

Alessandra Breschi ◽

Carrie A Davis ◽

Pablo Prieto Barja ◽

...

Keyword(s):

Gene Expression ◽

Mammalian Cells ◽

Cellular Localization ◽

Cell Types ◽

Evolutionary Constraint ◽

Novel Transcript ◽

Transcriptional Regulatory ◽

Mouse Tissues ◽

Mouse Transcriptome ◽

Transcriptional Output

We characterized by RNA-seq the transcriptional profiles of a large and heterogeneous collection of mouse tissues, augmenting the mouse transcriptome with thousands of novel transcript candidates. Comparison with transcriptome profiles obtained in human cell lines reveals substantial conservation of transcriptional programs, and uncovers a distinct class of genes with levels of expression across cell types and species, that have been constrained early in vertebrate evolution. This core set of genes capture a substantial and constant fraction of the transcriptional output of mammalian cells, and participates in basic functional and structural housekeeping processes common to all cell types. Perturbation of these constrained genes is associated with significant phenotypes including embryonic lethality and cancer. Evolutionary constraint in gene expression levels is not reflected in the conservation of the genomic sequences, but it is associated with strong and conserved epigenetic marking, as well as to a characteristic post-transcriptional regulatory program in which sub-cellular localization and alternative splicing play comparatively large roles.

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Effects of HTR1B 3' region polymorphisms and functional regions on gene expression regulation

10.21203/rs.3.rs-18106/v1 ◽

2020 ◽

Author(s):

xi xia ◽

Mei Ding ◽

Jin-feng Xuan ◽

Jia-xin Xing ◽

Hao Pang ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Regulation ◽

Inhibitory Effect ◽

Expression Level ◽

Luciferase Reporter ◽

Negative Effects ◽

Hek 293 ◽

Functional Regions ◽

Regulatory Effects ◽

Post Transcriptional Regulation

Abstract Background The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3' regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3' region of HTR1B. Methods Seven haplotypes, consisting of rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041, and truncated fragments of the HTR1B gene 3' region were transfected into SK-N-SH, HEK-293, and U87 cell lines. The relative fluorescence intensities were detected by a dual luciferase reporter assay system.Results We found that the haplotype, AG_CT_A, enhanced the expression level compared to the main haplotype; AG_CG_A; GG_CG_G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that +2440 ~ +2769 bp and +1953 ~ +2311 bp regions both had negative effects on gene expression.ConclusionsThe 3' region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3' region includes several effector binding sites that induce an inhibitory effect on gene expression.

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Transcriptome-wide in vivo mapping of cleavage sites for the compact cyanobacterial ribonuclease E reveals insights into its function and substrate recognition

10.1101/2021.07.27.453982 ◽

2021 ◽

Author(s):

Ute A. Hoffmann ◽

Florian Heyl ◽

Said N. Rogh ◽

Thomas Wallner ◽

Rolf Backofen ◽

...

Keyword(s):

Temperature Shift ◽

Temperature Sensitive ◽

Cleavage Sites ◽

Rnase E ◽

Ribonuclease E ◽

Regulatory Processes ◽

Transcriptional Regulatory ◽

Acting Mechanism ◽

Post Transcriptional Regulation

Ribonucleases are crucial enzymes in RNA metabolism and post-transcriptional regulatory processes in bacteria. Cyanobacteria encode the two essential ribonucleases RNase E and RNase J. Cyanobacterial RNase E is shorter than homologues in other groups of bacteria and lacks both the chloroplast-specific N-terminal extension as well as the C-terminal domain typical for RNase E of enterobacteria. In order to investigate the function of RNase E in the model cyanobacterium Synechocystis sp. PCC 6803, we engineered a temperature-sensitive RNase E mutant by introducing two site-specific mutations, I65F and spontaneously occurring V94A. This enabled us to perform RNA-seq after the transient inactivation of RNase E by a temperature shift (TIER-seq) and to map 1,472 RNase-E-dependent cleavage sites. We inferred a dominating cleavage signature consisting of an adenine at the -3 and a uridine at the +2 position within a single-stranded segment of the RNA. The data identified putative RNase-E-dependent instances of operon discoordination, mRNAs likely regulated jointly by RNase E and an sRNA, potential 3' end-derived sRNAs and a dual-acting mechanism for the glutamine riboswitch. Our findings substantiate the pivotal role of RNase E in post-transcriptional regulation and suggest the redundant or concerted action of RNase E and RNase J in cyanobacteria.

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A Unified Architecture of Transcriptional Regulatory Elements

10.1101/019844 ◽

2015 ◽

Author(s):

Robin Andersson ◽

Albin Sandelin ◽

Charles G Danko

Keyword(s):

Gene Expression ◽

Histone Modifications ◽

Transcription Initiation ◽

Regulatory Elements ◽

Functional Element ◽

Gene Promoters ◽

Single Class ◽

Transcriptional Regulatory Elements ◽

Transcriptional Regulatory ◽

Transcriptional Output

Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However, recent studies have revealed broad similarities between enhancers and promoters, blurring the distinction: active enhancers often initiate transcription, and some gene promoters have the potential of enhancing transcriptional output of other promoters. Here, we propose a model in which promoters and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements, and surrounding sequences, determine local transcriptional output as well as the enhancer and promoter activities of individual elements.

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