Structural Insights into RNA Dimerization: Motifs, Interfaces and Functions

In comparison with the pervasive use of protein dimers and multimers in all domains of life, functional RNA oligomers have so far rarely been observed in nature. Their diminished occurrence contrasts starkly with the robust intrinsic potential of RNA to multimerize through long-range base-pairing (“kissing”) interactions, self-annealing of palindromic or complementary sequences, and stable tertiary contact motifs, such as the GNRA tetraloop-receptors. To explore the general mechanics of RNA dimerization, we performed a meta-analysis of a collection of exemplary RNA homodimer structures consisting of viral genomic elements, ribozymes, riboswitches, etc., encompassing both functional and fortuitous dimers. Globally, we found that domain-swapped dimers and antiparallel, head-to-tail arrangements are predominant architectural themes. Locally, we observed that the same structural motifs, interfaces and forces that enable tertiary RNA folding also drive their higher-order assemblies. These feature prominently long-range kissing loops, pseudoknots, reciprocal base intercalations and A-minor interactions. We postulate that the scarcity of functional RNA multimers and limited diversity in multimerization motifs may reflect evolutionary constraints imposed by host antiviral immune surveillance and stress sensing. A deepening mechanistic understanding of RNA multimerization is expected to facilitate investigations into RNA and RNP assemblies, condensates, and granules and enable their potential therapeutical targeting.

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Crystal structure of Pistol, a class of self-cleaving ribozyme

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1611191114 ◽

2017 ◽

Vol 114 (5) ◽

pp. 1021-1026 ◽

Cited By ~ 32

Author(s):

Laura A. Nguyen ◽

Jimin Wang ◽

Thomas A. Steitz

Keyword(s):

Crystal Structure ◽

Rna Structure ◽

Tertiary Structure ◽

Genomic Analysis ◽

Comparative Genomic ◽

Nonbridging Oxygen ◽

Close Proximity ◽

Domains Of Life ◽

Guanine Base ◽

A Minor

Small self-cleaving ribozymes have been discovered in all evolutionary domains of life. They can catalyze site-specific RNA cleavage, and as a result, they have relevance in gene regulation. Comparative genomic analysis has led to the discovery of a new class of small self-cleaving ribozymes named Pistol. We report the crystal structure of Pistol at 2.97-Å resolution. Our results suggest that the Pistol ribozyme self-cleavage mechanism likely uses a guanine base in the active site pocket to carry out the phosphoester transfer reaction. The guanine G40 is in close proximity to serve as the general base for activating the nucleophile by deprotonating the 2′-hydroxyl to initiate the reaction (phosphoester transfer). Furthermore, G40 can also establish hydrogen bonding interactions with the nonbridging oxygen of the scissile phosphate. The proximity of G32 to the O5′ leaving group suggests that G32 may putatively serve as the general acid. The RNA structure of Pistol also contains A-minor interactions, which seem to be important to maintain its tertiary structure and compact fold. Our findings expand the repertoire of ribozyme structures and highlight the conserved evolutionary mechanism used by ribozymes for catalysis.

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Phytoplankton thermal responses adapt in the absence of hard thermodynamic constraints

10.1101/452250 ◽

2018 ◽

Cited By ~ 1

Author(s):

Dimitrios - Georgios Kontopoulos ◽

Erik van Sebille ◽

Michael Lange ◽

Gabriel Yvon-Durocher ◽

Timothy G. Barraclough ◽

...

Keyword(s):

Thermal Performance ◽

Thermal Sensitivity ◽

Meta Analysis ◽

Habitat Type ◽

Performance Curve ◽

Thermal Environments ◽

Thermal Performance Curve ◽

Performance Curves ◽

Minor Influence ◽

A Minor

AbstractTo better predict how populations and communities respond to climatic temperature variation, it is necessary to understand how the shape of the response of fitness-related traits to temperature evolves (the thermal performance curve). Currently, there is disagreement about the extent to which the evolution of thermal performance curves is constrained. One school of thought has argued for the prevalence of thermodynamic constraints through enzyme kinetics, whereas another argues that adaptation can—at least partly—overcome such constraints. To shed further light on this debate, we perform a phylogenetic meta-analysis of the thermal performance curves of growth rate of phytoplankton—a globally important functional group—, controlling for environmental effects (habitat type and thermal regime). We find that thermodynamic constraints have a minor influence on the shape of the curve. In particular, we detect a very weak increase of maximum performance with the temperature at which the curve peaks, suggesting a weak “hotter-is-better” constraint. Also, instead of a constant thermal sensitivity of growth across species, as might be expected from strong constraints, we find that all aspects of the thermal performance curve evolve along the phylogeny. Our results suggest that phytoplankton thermal performance curves adapt to thermal environments largely in the absence of hard thermodynamic constraints.

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Human PRE-PIK3C2B exhibits long-range intra- and inter-chromosomal interactions with genomic regions enriched in repressive marks

10.1101/2020.11.11.378745 ◽

2020 ◽

Author(s):

Jayant Maini ◽

Ankit Kumar Pathak ◽

Kausik Bhattacharyya ◽

Narendra Kumar ◽

Ankita Narang ◽

...

Keyword(s):

Long Range ◽

Meta Analysis ◽

Range Interaction ◽

Dual Nature ◽

Polycomb Response Element ◽

Chromatin Interactions ◽

Long Range Interaction ◽

Intergenic Regions ◽

Genomic Regions ◽

Transcriptional Start Sites

AbstractHuman PRE-PIK3C2B is a dual nature polycomb response element that interacts with both polycomb as well as trithorax members. In the current study, using 4C-Seq (Capturing Circular Chromosomal Conformation-Sequencing), we identified long-range chromatin interactions associated with PRE-PIK3C2B and validated them with 3C-PCR. We identified both intra-as well as inter-chromosomal interactions, a large proportion of which were found to be closely distributed around transcriptional start sites (TSS). A significant number of interactions were also found to be associated with heterochromatic regions. Meta-analysis of ENCODE ChIP-Seq data identified an overall enrichment of YY1, CTCF as well as histone modification such as H3K4me3 and H3K27me marks in different cell lines. Almost 90% interactions were derived from either intronic or intergenic regions. among which large proportions of intronic interactors were either unique sequences or LINE/SINE derived. In case of intergenic interactions, majority of the interaction were associated with LINE/SINE repeats. We further found that genes proximal to the interactor sequences were co-expressed, they showed reduced expression. To the best of our knowledge this is one of the early demonstrations of long-range interaction of PRE sequences in human genome.

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Chemical Shift. VII. The Long-range Shielding Effects of the Cyano Group

Canadian Journal of Chemistry ◽

10.1139/v72-373 ◽

1972 ◽

Vol 50 (14) ◽

pp. 2351-2356 ◽

Cited By ~ 14

Author(s):

J. W. ApSimon ◽

H. Beierbeck ◽

D. K. Todd

Keyword(s):

Chemical Shift ◽

Long Range ◽

Field Effect ◽

Cyano Group ◽

Electric Field Effect ◽

Minor Contribution ◽

Anisotropy Effect ◽

A Minor ◽

Good Agreement ◽

Shielding Effects

Using the methods described in parts I–VI of this series, we have examined the long-range shielding effects of the cyano group upon the C-18 and -19 methyl protons in several cyano-steroids and the ring protons in 2-endo- and 2-exo-cyanonorbornenes.It was found that the most important shielding mechanism of the cyano group is its electric field effect, with the magnetic anisotropy effect making at most a minor contribution to the screening. However, only in the cases of the cyano-steroids was good agreement obtained between the calculated and the experimental shifts.

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Surfactant-directed syntheses of mesostructured zinc imidazolates: formation mechanism and structural insights

CrystEngComm ◽

10.1039/c4ce01512f ◽

2015 ◽

Vol 17 (2) ◽

pp. 463-470 ◽

Cited By ~ 10

Author(s):

E. A. Flügel ◽

M. T. Aronson ◽

S. C. Junggeburth ◽

B. F. Chmelka ◽

B. V. Lotsch

Keyword(s):

Long Range ◽

Formation Mechanism ◽

Lamellar Zinc ◽

Structural Insights

A detailed study on the formation mechanism, local and long-range structures of surfactant-directed lamellar zinc imidazolates is presented.

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Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: a systematic review and meta-analysis

Infectious Diseases of Poverty ◽

10.1186/s40249-021-00915-3 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Qiao Liu ◽

Chenyuan Qin ◽

Min Liu ◽

Jue Liu

Keyword(s):

Adverse Events ◽

Incidence Rate ◽

Real World ◽

Fixed Effects ◽

Meta Analysis ◽

Immune Surveillance ◽

Herd Immunity ◽

Vaccine Safety ◽

Vaccine Effectiveness ◽

Alpha Variant

Abstract Background To date, coronavirus disease 2019 (COVID-19) becomes increasingly fierce due to the emergence of variants. Rapid herd immunity through vaccination is needed to block the mutation and prevent the emergence of variants that can completely escape the immune surveillance. We aimed to systematically evaluate the effectiveness and safety of COVID-19 vaccines in the real world and to establish a reliable evidence-based basis for the actual protective effect of the COVID-19 vaccines, especially in the ensuing waves of infections dominated by variants. Methods We searched PubMed, Embase and Web of Science from inception to July 22, 2021. Observational studies that examined the effectiveness and safety of SARS-CoV-2 vaccines among people vaccinated were included. Random-effects or fixed-effects models were used to estimate the pooled vaccine effectiveness (VE) and incidence rate of adverse events after vaccination, and their 95% confidence intervals (CI). Results A total of 58 studies (32 studies for vaccine effectiveness and 26 studies for vaccine safety) were included. A single dose of vaccines was 41% (95% CI: 28–54%) effective at preventing SARS-CoV-2 infections, 52% (31–73%) for symptomatic COVID-19, 66% (50–81%) for hospitalization, 45% (42–49%) for Intensive Care Unit (ICU) admissions, and 53% (15–91%) for COVID-19-related death; and two doses were 85% (81–89%) effective at preventing SARS-CoV-2 infections, 97% (97–98%) for symptomatic COVID-19, 93% (89–96%) for hospitalization, 96% (93–98%) for ICU admissions, and 95% (92–98%) effective for COVID-19-related death, respectively. The pooled VE was 85% (80–91%) for the prevention of Alpha variant of SARS-CoV-2 infections, 75% (71–79%) for the Beta variant, 54% (35–74%) for the Gamma variant, and 74% (62–85%) for the Delta variant. The overall pooled incidence rate was 1.5% (1.4–1.6%) for adverse events, 0.4 (0.2–0.5) per 10 000 for severe adverse events, and 0.1 (0.1–0.2) per 10 000 for death after vaccination. Conclusions SARS-CoV-2 vaccines have reassuring safety and could effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world. In the context of global pandemic and the continuous emergence of SARS-CoV-2 variants, accelerating vaccination and improving vaccination coverage is still the most important and urgent matter, and it is also the final means to end the pandemic. Graphical Abstract

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Engineering long-range interactions between ultracold atoms with light

Journal of Physics B Atomic Molecular and Optical Physics ◽

10.1088/1361-6455/ac4b40 ◽

2022 ◽

Author(s):

Ting XIE ◽

Andrea Orbán ◽

Xiaodong Xing ◽

Eliane Luc-Koenig ◽

Romain Vexiau ◽

...

Keyword(s):

Long Range ◽

Ultracold Atoms ◽

Quantum Gases ◽

Atomic Gases ◽

Complete Suppression ◽

Atomic Collisions ◽

Range Interaction ◽

Long Range Interactions ◽

To Come ◽

A Minor

Abstract Ultracold temperatures in dilute quantum gases opened the way to an exquisite control of matter at the quantum level. Here we focus on the control of ultracold atomic collisions using a laser to engineer their interactions at large interatomic distances. We show that the entrance channel of two colliding ultracold atoms can be coupled to a repulsive collisional channel by the laser light so that the overall interaction between the two atoms becomes repulsive: this prevents them to come close together and to undergo inelastic processes, thus protecting the atomic gases from unwanted losses. We illustrate such an optical shielding mechanism with 39K and 133Cs atoms colliding at ultracold temperature (<1 microkelvin). The process is described in the framework of the dressed-state picture and we then solve the resulting stationary coupled Schrödinger equations. The role of spontaneous emission and photoinduced inelastic scattering is also investigated as possible limitations of the shielding efficiency. We predict an almost complete suppression of inelastic collisions over a broad range of Rabi frequencies and detunings from the 39K D2 line of the optical shielding laser, both within the [0, 200 MHz] interval. We found that the polarization of the shielding laser has a minor influence on this efficiency. This proposal could easily be formulated for other bialkali-metal pairs as their long-range interaction are all very similar to each other.

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Selective exposure in action: Do visitors of product evaluation portals select reviews in a biased manner?

Cyberpsychology Journal of Psychosocial Research on Cyberspace ◽

10.5817/cp2021-1-4 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Kevin Winter ◽

Birka Zapf ◽

Mandy Hütter ◽

Nicolas Tichy ◽

Kai Sassenberg

Keyword(s):

Meta Analysis ◽

Product Evaluation ◽

Selective Exposure ◽

Minor Role ◽

Interface Properties ◽

Industrialized Countries ◽

Information Selection ◽

Total N ◽

Initial Preference ◽

A Minor

Most people in industrialized countries regularly purchase products online. Consumers often rely on previous customers’ reviews to make purchasing decisions. The current research investigates whether potential online customers select these reviews in a biased way and whether typical interface properties of product evaluation portals foster biased selection. Based on selective exposure research, potential online customers should have a bias towards selecting positive reviews when they have an initial preference for a product. We tested this prediction across five studies (total N = 1376) while manipulating several typical properties of the review selection interface that should – according to earlier findings – facilitate biased selection. Across all studies, we found some evidence for a bias in favor of selecting positive reviews, but the aggregated effect was non-significant in an internal meta-analysis. Contrary to our hypothesis and not replicating previous research, none of the interface properties that were assumed to increase biased selection led to the predicted effects. Overall, the current research suggests that biased information selection, which has regularly been found in many other contexts, only plays a minor role in online review selection. Thus, there is no need to fear that product evaluation portals elicit biased impressions about products among consumers due to selective exposure.

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Targeting Cancer Stem Cells—A Renewed Therapeutic Paradigm

Oncology & Hematology Review (US) ◽

10.17925/ohr.2017.13.01.45 ◽

2017 ◽

Vol 13 (01) ◽

pp. 45

Author(s):

Catherine L Amey ◽

Antoine E Karnoub ◽

◽

Keyword(s):

Stem Cells ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Residual Disease ◽

Immune Surveillance ◽

Tumor Initiating Cells ◽

Primary Tumors ◽

Cancer Management ◽

After Cancer ◽

A Minor

Metastasis is often accompanied by radio- and chemotherapeutic resistance to anticancer treatments and is the major cause of death in cancer patients. Better understanding of how cancer cells circumvent therapeutic insults and how disseminated cancer clones generate life-threatening metastases would therefore be paramount to the development of effective therapeutic approaches for clinical management of malignant disease. Mounting reports over the past two decades have provided evidence for the existence of a minor population of highly malignant cells within liquid and solid tumors, which are capable of self-renewing and of regenerating secondary growths with the heterogeneity of the primary tumors from which they derive. These cells, called tumor-initiating cells or cancer stem cells (CSCs) exhibit increased resistance to standard radio- and chemotherapies and appear to have mechanisms that enable them to evade immune surveillance. CSCs are therefore considered to be responsible for systemic residual disease after cancer therapy, as well as for disease relapse. How CSCs develop, the nature of the interactions they establish with their microenvironment, their phenotypic and functional characteristics, as well as their molecular dependencies have all taken center stage in cancer therapy. Indeed, improved understanding of CSC biology is critical to the development of important CSC-based anti-neoplastic approaches that have the potential to radically improve cancer management. Here, we summarize some of the most pertinent elements regarding CSC development and properties, and highlight some of the clinical modalities in current development as anti-CSC therapeutics.

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