scholarly journals Cooperativity and Interdependency between RNA Structure and RNA–RNA Interactions

2021 ◽  
Vol 7 (4) ◽  
pp. 81
Author(s):  
Ilias Skeparnias ◽  
Jinwei Zhang
Keyword(s):  
Rna Structure ◽  
Noncoding Rna ◽  
Quaternary Structure ◽  
Reciprocal Relationship ◽  
Rna Structures ◽  
Granule Formation ◽  
Expression Control ◽  
Gene Expression Control ◽  
Transcription Complexes ◽  
Rna Complexes

Complex RNA–RNA interactions are increasingly known to play key roles in numerous biological processes from gene expression control to ribonucleoprotein granule formation. By contrast, the nature of these interactions and characteristics of their interfaces, especially those that involve partially or wholly structured RNAs, remain elusive. Herein, we discuss different modalities of RNA–RNA interactions with an emphasis on those that depend on secondary, tertiary, or quaternary structure. We dissect recently structurally elucidated RNA–RNA complexes including RNA triplexes, riboswitches, ribozymes, and reverse transcription complexes. These analyses highlight a reciprocal relationship that intimately links RNA structure formation with RNA–RNA interactions. The interactions not only shape and sculpt RNA structures but also are enabled and modulated by the structures they create. Understanding this two-way relationship between RNA structure and interactions provides mechanistic insights into the expanding repertoire of noncoding RNA functions, and may inform the design of novel therapeutics that target RNA structures or interactions.

scholarly journals HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Jessica Rea ◽  
Valentina Menci ◽  
Paolo Tollis ◽  
Tiziana Santini ◽  
Alexandros Armaos ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Cell Fate ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Cascade ◽  
Expression Control ◽  
Gene Expression Control

Abstract Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The sequential activation/repression of genes driving cell fate specification is achieved by complex regulatory networks, where transcription factors and noncoding RNAs work in a coordinated manner. Herein, we identify the long noncoding RNA HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1) as a new player in neuronal differentiation. We demonstrate that the neuronal-enriched HOTAIRM1 isoform epigenetically controls the expression of the proneural transcription factor NEUROGENIN 2 that is key to neuronal fate commitment and critical for brain development. We also show that HOTAIRM1 activity impacts on NEUROGENIN 2 downstream regulatory cascade, thus contributing to the achievement of proper neuronal differentiation timing. Finally, we identify the RNA-binding proteins HNRNPK and FUS as regulators of HOTAIRM1 biogenesis and metabolism. Our findings uncover a new regulatory layer underlying NEUROGENIN 2 transitory expression in neuronal differentiation and reveal a previously unidentified function for the neuronal-induced long noncoding RNA HOTAIRM1.

scholarly journals Methods for the analysis of transcriptome dynamics

2019 ◽  
Vol 8 (5) ◽  
pp. 597-612 ◽  
Author(s):  
Daniela F. Rodrigues ◽  
Vera M. Costa ◽  
Ricardo Silvestre ◽  
Maria L. Bastos ◽  
Félix Carvalho
Keyword(s):  
Gene Expression ◽  
Transcriptome Analysis ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Gene Expression Regulation ◽  
System Level ◽  
Rna Transcription ◽  
Expression Control ◽  
Gene Expression Control ◽  
Gene Expression Alterations

Abstract The transcriptome is the complete set of transcripts in a cell or tissue and includes ribosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and regulatory noncoding RNA. At steady-state, the transcriptome results from a compensatory variation of the transcription and decay rate to maintain the RNA concentration constant. RNA transcription constitutes the first stage in gene expression, and thus is a major and primary mode of gene expression control. Nevertheless, regulation of RNA decay is also a key factor in gene expression control, involving either selective RNA stabilization or enhanced degradation. Transcriptome analysis allows the identification of gene expression alterations, providing new insights regarding the pathways and mechanisms involved in physiological and pathological processes. Upon perturbation of cell homeostasis, rapid changes in gene expression are required to adapt to new conditions. Thus, to better understand the regulatory mechanisms associated with gene expression alterations, it is vital to acknowledge the relative contribution of RNA synthesis and decay to the transcriptome. To the toxicology field, the study of gene expression regulation mechanisms can help identify the early and mechanistic relevant cellular events associated with a particular response. This review aims to provide a critical comparison of the available methods used to analyze the contribution of RNA transcription and decay to gene expression dynamics. Notwithstanding, an integration of the data obtained is necessary to understand the entire repercussions of gene transcription changes at a system-level. Thus, a brief overview of the methods available for the integration and analysis of the data obtained from transcriptome analysis will also be provided.

scholarly journals RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Erich G Chapman ◽  
Stephanie L Moon ◽  
Jeffrey Wilusz ◽  
Jeffrey S Kieft
Keyword(s):  
Dengue Virus ◽  
Rna Structure ◽  
Noncoding Rna ◽  
Rna Folding ◽  
Rna Degradation ◽  
Rna Structures ◽  
Genomic Rna ◽  
Virus Rna ◽  
Folded Rna ◽  
Viral Genomic Rna

Dengue virus is a growing global health threat. Dengue and other flaviviruses commandeer the host cell’s RNA degradation machinery to generate the small flaviviral RNA (sfRNA), a noncoding RNA that induces cytopathicity and pathogenesis. Host cell exonuclease Xrn1 likely loads on the 5′ end of viral genomic RNA and degrades processively through ∼10 kB of RNA, halting near the 3′ end of the viral RNA. The surviving RNA is the sfRNA. We interrogated the architecture of the complete Dengue 2 sfRNA, identifying five independently-folded RNA structures, two of which quantitatively confer Xrn1 resistance. We developed an assay for real-time monitoring of Xrn1 resistance that we used with mutagenesis and RNA folding experiments to show that Xrn1-resistant RNAs adopt a specific fold organized around a three-way junction. Disrupting the junction’s fold eliminates the buildup of disease-related sfRNAs in human cells infected with a flavivirus, directly linking RNA structure to sfRNA production.

scholarly journals RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures

2021 ◽  
Vol 49 (6) ◽  
pp. 3409-3426
Author(s):  
Arancha Catalan-Moreno ◽  
Marta Cela ◽  
Pilar Menendez-Gil ◽  
Naiara Irurzun ◽  
Carlos J Caballero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rna Structure ◽  
Cold Shock ◽  
Mrna Translation ◽  
Site Directed Mutagenesis ◽  
Rna Structures ◽  
Double Stranded Rna ◽  
Ambient Temperatures ◽  
Shock Proteins ◽  
Rna Hairpin

Abstract Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches. Through in silico prediction, enzymatic probing and site-directed mutagenesis, we demonstrated that cspB and cspC 5′UTRs adopt alternative RNA structures that shift from one another upon temperature shifts. The open (O) conformation that facilitates mRNA translation is favoured at ambient temperatures (22°C). Conversely, the alternative locked (L) conformation, where the ribosome binding site (RBS) is sequestered in a double-stranded RNA structure, is folded at host-related temperatures (37°C). These structural rearrangements depend on a long RNA hairpin found in the O conformation that sequesters the anti-RBS sequence. Notably, the remaining S. aureus CSP, CspA, may interact with a UUUGUUU motif located in the loop of this long hairpin and favour the folding of the L conformation. This folding represses CspB and CspC production at 37°C. Simultaneous deletion of the cspB/cspC genes or their RNA thermoswitches significantly decreases S. aureus growth rate at ambient temperatures, highlighting the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment.

scholarly journals Transcriptomic uniqueness and commonality of the ion channels and transporters in the four heart chambers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sanda Iacobas ◽  
Bogdan Amuzescu ◽  
Dumitru A. Iacobas
Keyword(s):  
Ion Channels ◽  
Cycle Phase ◽  
Functional Roles ◽  
Expression Control ◽  
Gene Expression Control ◽  
Left And Right ◽  
The Right ◽  
Phase Out ◽  
Right Atria ◽  
Agilent Microarrays

AbstractMyocardium transcriptomes of left and right atria and ventricles from four adult male C57Bl/6j mice were profiled with Agilent microarrays to identify the differences responsible for the distinct functional roles of the four heart chambers. Female mice were not investigated owing to their transcriptome dependence on the estrous cycle phase. Out of the quantified 16,886 unigenes, 15.76% on the left side and 16.5% on the right side exhibited differential expression between the atrium and the ventricle, while 5.8% of genes were differently expressed between the two atria and only 1.2% between the two ventricles. The study revealed also chamber differences in gene expression control and coordination. We analyzed ion channels and transporters, and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/gluconeogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 oscillates in phase with all 27 quantified binding partners in the left ventricle, the percentage of in-phase oscillating partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis indicated high interventricular synchrony of the ion channels expressions and the substantially lower synchrony between the two atria and between the atrium and the ventricle from the same side.

scholarly journals High-performance chemical- and light-inducible recombinases in mammalian cells and mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin H. Weinberg ◽  
Jang Hwan Cho ◽  
Yash Agarwal ◽  
N. T. Hang Pham ◽  
Leidy D. Caraballo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
High Performance ◽  
Genome Engineering ◽  
Genetic Circuits ◽  
Control Of Gene Expression ◽  
Expression Control ◽  
Gene Expression Control ◽  
High Performance Systems ◽  
Spatiotemporal Control

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.

Sign in / Sign up

Export Citation Format

Share Document