scholarly journals Genome-wide RNA structure changes during human neurogenesis drive gene regulatory networks

2021 ◽  
Author(s):  
Jiaxu Wang ◽  
Tong Zhang ◽  
Yu Zhang ◽  
Wen Ting Tan ◽  
Roland G Huber ◽  
...  
Keyword(s):  
Human Development ◽  
Rna Structure ◽  
Regulatory Networks ◽  
Rna Structures ◽  
Differentiated Cells ◽  
Structure Changes ◽  
Specific Regulation ◽  
Dynamics And Function ◽  
Drive Gene ◽  
And Function

The distribution, dynamics and function of RNA structures in human development is under-explored. Here, we systematically assayed RNA structural dynamics and its relationship with gene expression, translation and decay during human neurogenesis. We observed that the human ESC transcriptome is globally more structurally accessible than that of differentiated cells; and undergo extensive RNA structure changes, particularly in the 3UTR. Additionally, RNA structure changes during differentiation is associated with translation and decay. We also identified stage-specific regulation as RBP and miRNA binding, as well as splicing is associated with structure changes during early and late differentiation, respectively. Further, RBPs serve as a major factor in structure remodelling and co-regulates additional RBPs and miRNAs through structure. We demonstrated an example of this by showing that PUM2-induced structure changes on LIN28A enable miR-30 binding. This study deepens our understanding of the wide-spread and complex role of RNA-based gene regulation during human development.

scholarly journals Nup93 and CTCF co-modulate spatiotemporal dynamics and function of the HOXA gene cluster during differentiation

2019 ◽  
Author(s):  
Ajay S. Labade ◽  
Adwait Salvi ◽  
Krishanpal Karmodiya ◽  
Kundan Sengupta
Keyword(s):  
Gene Expression ◽  
Gene Locus ◽  
Nuclear Periphery ◽  
Spatiotemporal Dynamics ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Dynamics And Function ◽  
Hoxa Gene Expression ◽  
And Function ◽  
Hoxa Gene

ABSTRACTNucleoporins regulate nuclear transport. In addition, nucleoporins also modulate chromatin organization and gene expression. Here we investigated the role of nucleoporin Nup93, in regulating HOXA gene expression during differentiation. ChIP-Seq analysis revealed that Nup93 associates with genes involved in development and differentiation. Furthermore, Nup93 occupancy significantly overlaps with CTCF. Interestingly, Nup93 and CTCF show antagonistic roles in regulating 3’ and 5’ end HOXA genes in undifferentiated cells. The HOXA gene locus untethered from the nuclear periphery upon Nup93 but not CTCF depletion, consistent with its upregulation. Remarkably, occupancy of Nup93 and CTCF on HOXA gene locus progressively declined during differentiation but was restored in differentiated cells, consistent with the rerepression and re-localization of the HOXA gene locus with the nuclear periphery upon differentiation. In summary, Nup93 is a key modulator of the spatiotemporal dynamics and function of the HOXA gene locus during differentiation.

scholarly journals CoDNaS-RNA: a database of Conformational Diversity in the Native State of RNA

2020 ◽  
Author(s):  
Martín González Buitrón ◽  
Ronaldo Romario Tunque Cahui ◽  
Emilio García Ríos ◽  
Layla Hirsh ◽  
María Silvina Fornasari ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Features ◽  
Rna Structures ◽  
Rna Molecules ◽  
Functional Annotations ◽  
Public Resource ◽  
Conformational Diversity ◽  
Dynamics And Function ◽  
And Function ◽  
The Relationship

AbstractConformational changes in RNA native ensembles are central to fulfill many of their biological roles. Systematic knowledge of the extent and possible modulators of this conformational diversity is desirable to better understand the relationship between RNA dynamics and function.We have developed CoDNaS-RNA as the first database of conformational diversity in RNA molecules. Known RNA structures are retrieved and clustered to identify alternative conformers of each molecule. Pairwise structural comparisons within each cluster allows to measure the variability of the molecule. Additional data on structural features, molecular interactions and functional annotations are provided. CoDNaS-RNA is implemented as a public resource that can be of much interest for computational and bench scientists alike.AvailabilityCoDNaS-RNA is freely accessible at http://ufq.unq.edu.ar/[email protected]

scholarly journals A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in humans

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Miguel Casanova ◽  
Madeleine Moscatelli ◽  
Louis Édouard Chauvière ◽  
Christophe Huret ◽  
Julia Samson ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Endogenous Retroviruses ◽  
X Chromosomes ◽  
Regulatory Pathways ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Specific Regulation ◽  
Species Specific ◽  
And Function

AbstractTransposable elements (TEs) have been proposed to play an important role in driving the expansion of gene regulatory networks during mammalian evolution, notably by contributing to the evolution and function of long non-coding RNAs (lncRNAs). XACT is a primate-specific TE-derived lncRNA that coats active X chromosomes in pluripotent cells and may contribute to species-specific regulation of X-chromosome inactivation. Here we explore how different families of TEs have contributed to shaping the XACT locus and coupling its expression to pluripotency. Through a combination of sequence analysis across primates, transcriptional interference, and genome editing, we identify a critical enhancer for the regulation of the XACT locus that evolved from an ancestral group of mammalian endogenous retroviruses (ERVs), prior to the emergence of XACT. This ERV was hijacked by younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways.

Fluorescent ribonucleoside analogues as probes for investigating RNA structure and function

2010 ◽  
Vol 83 (1) ◽  
pp. 213-232 ◽  
Author(s):  
Seergazhi G. Srivatsan ◽  
Anupam A. Sawant
Keyword(s):  
Nucleic Acid ◽  
Conformational Changes ◽  
Rna Structure ◽  
Photophysical Properties ◽  
Local Environment ◽  
Spectroscopic Techniques ◽  
Rna Structures ◽  
Base Pairs ◽  
Target Nucleic Acid ◽  
And Function

Numerous biophysical tools based on fluorescence have been developed to advance the understanding of RNA–nucleic acid, RNA–protein, and RNA–small molecule inter-actions. In this regard, fluorescent ribonucleoside analogues that are sensitive to their local environment provide sensitive probes for investigating RNA structure, dynamics, and recognition. Most of these analogues closely resemble the native ribonucleosides with respect to their overall dimension and have the ability to form canonical Watson–Crick (WC) base pairs. Therefore, it is possible to place these probes near the point of interaction in a target nucleic acid with minimum structural perturbations and gain insight into the intricacies of conformational changes taking place in and around the interaction site. Here, we provide a concise background on the development and recent advances in the applications of base-modified fluorescent ribonucleoside analogue probes. We first present various base-modified fluorescent ribonucleoside analogues, their photophysical properties, and methods to incorporate these analogues into oligoribonucleotides. We then discuss the established spectroscopic techniques, which make use of the fluorescence properties of these emissive ribonucleoside analogues. Finally, we present the applications of base-modified fluorescent ribonucleoside analogues used as probes incorporated into oligoribonucleotides in investigating RNA structures and functions.

Wisdom and culture

2017 ◽  
Author(s):  
Igor Grossmann ◽  
Franki Y. H. Kung
Keyword(s):  
Human Development ◽  
Cross Cultural ◽  
Folk Beliefs ◽  
Psychological Phenomena ◽  
Culturally Grounded ◽  
Pragmatic Reasoning ◽  
And Function ◽  
Social Components

Wisdom is often considered to be the pinnacle of human development. Though it is universally cherished, it is unclear whether the concept of wisdom can be applied similarly across cultures. We review the emerging research on this topic, exploring extant scholarly definitions, portrayals of wisdom in the world’s philosophies, folk beliefs concerning wisdom and its development, and empirical insights evaluating expression of wisdom-related characteristics. There appears to be a large amount of convergence in scholarly and cross-cultural folk concepts, suggesting that wisdom involves certain aspects of pragmatic reasoning, with less clarity concerning emotion regulatory and prosocial aspects of wisdom. Folk beliefs about wisdom vary across cultures in the degree to which they emphasize social components and characterize development of wisdom as an incremental ability (vs. an immutable entity). Cultures also vary in the likelihood of expressing wisdom. We conclude by calling for a culturally-grounded understanding of the distribution and function of wisdom-related psychological phenomena.

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.

Sign in / Sign up

Export Citation Format

Share Document