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Topic Review
RNA-Binding Proteins Regulating
The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. The post-transcriptional regulation of lncRNAs is mediated by RNA-binding proteins (RBPs). Interestingly, RBPs themselves are commonly deregulated in cancer and could thus constitute a major contribution to the deregulation of cancer-associated lncRNAs. Discussed here are four examples of well-known RBPs that regulate the transport or localization of cancer-associated lncRNAs and thereby impact the functionality of these lncRNAs. So far, out of the vast number of RBPs that exist, only a relatively small number has been found to specifically guide the transport or localization of cancer-related lncRNAs. In general, there is still a lack of knowledge about how lncRNAs are shuttled between or retained within different cellular compartments and future research will have to shed more light on these regulatory mechanisms.
  • 835
  • 29 Oct 2020
Topic Review
RNA-Binding Protein Rbm24
Rbm24 (RNA-binding motif protein 24) is an evolutionarily conserved RBP that contains a single RNA recognition motif (RRM) at its N-terminal region [13–15]. It exhibits strongly restricted tissue-specific expression patterns during vertebrate development [16], and emerges as an important regulator of cellular differentiation and a potential factor implicated in human disease. Rbm24 gene exhibits strongly conserved expression in the somites, heart, lens and otic vesicle of all vertebrate embryos. It is involved in different aspects of post-transcriptional regulation of gene expression, including pre-mRNA alternative splicing, mRNA stability and polyadenylation. Knockout of this gene in mice and zebrafish causes severe developmental defects, such as heart malformations, cataract formation and hearing deficits.
  • 584
  • 27 Oct 2020
Topic Review
RNA Vaccine
A ribonucleic acid (RNA) vaccine or messenger RNA (mRNA) vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine transfects molecules of synthetic RNA into immune cells, where the vaccine functions as mRNA, causing the cells to build foreign protein that would normally be produced by a pathogen (such as a virus) or by a cancer cell. These protein molecules stimulate an adaptive immune response which teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles which protect the RNA strands and help their absorption into the cells. Reactogenicity, the tendency of a vaccine to produce adverse reactions, is similar to that of conventional non-RNA vaccines. People susceptible to an autoimmune response may have an adverse reaction to RNA vaccines. The advantages of RNA vaccines over traditional protein vaccines are ease of design, speed and lower cost of production, and the induction of both cellular and humoral immunity. RNA vaccines, such as the Pfizer–BioNTech COVID-19 vaccine, have the disadvantage of requiring ultracold storage before distribution; other mRNA vaccines, such as the Moderna, CureVac, and Walvax COVID-19 vaccines, do not require such ultracold storage temperatures. In RNA therapeutics, mRNA vaccines have attracted considerable interest as COVID-19 vaccines. In December 2020, Pfizer–BioNTech and Moderna obtained approval for their mRNA-based COVID-19 vaccines. On 2 December, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) became the first medicines regulator to approve an mRNA vaccine, authorizing the Pfizer–BioNTech vaccine for widespread use. On 11 December, the US Food and Drug Administration (FDA) issued an emergency use authorization for the Pfizer–BioNTech vaccine and a week later similarly approved the Moderna vaccine. The use of RNA in vaccines has occasioned substantial misinformation in social media, wrongly claiming that the introduction of RNA alters a person's DNA.
  • 1.1K
  • 18 Oct 2022
Topic Review
RNA Modifications in Translation Fidelity
RNA modifications play an essential role in determining RNA fate. Recent studies have revealed the effects of such modifications on all steps of RNA metabolism. These modifications range from the addition of simple groups, such as methyl groups, to the addition of highly complex structures, such as sugars. Their consequences for translation fidelity are not always well documented. Unlike the well-known m6A modification, they are thought to have direct effects on either the folding of the molecule or the ability of tRNAs to bind their codons.
  • 683
  • 19 Nov 2021
Topic Review
Rieske Iron-Sulfur Protein in COPD and Pulmonary Hypertension
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide. The development of pulmonary hypertension (PH) accounts for the high mortality rate in COPD patients. Recent studies from the researchers' laboratory and others have highlighted the important role of reactive oxygen species (ROS) signaling in the development of COPD and associated PH. ROS are primarily generated in mitochondrial complex III in pulmonary artery smooth muscle cells (PASMCs). Rieske iron-sulfur protein (RISP), a catalytic subunit of mitochondrial complex III, is the major player in the generation of ROS. RISP plays a critical role in pulmonary vasoconstriction, remodeling, and hypertension.
  • 453
  • 17 Nov 2022
Topic Review
Ribosome Interactions with SARS-CoV-2 and COVID-19 mRNA Vaccine
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis. Viral nonstructural proteins (NSPs) interact with a range of different ribosomal states and interfere with mRNA translation. Concurrent mutations on NSPs and spike proteins contribute to the epidemiological success of variants of concern (VOCs). The interactions between ribosomes and SARS-CoV-2 represent attractive targets for the development of antiviral therapeutics and vaccines.
  • 633
  • 18 Feb 2022
Topic Review
Ribosomal Protein L10
Eukaryotic cytoplasmic ribosomes are highly structured macromolecular complexes made up of four different ribosomal RNAs (rRNAs) and 80 ribosomal proteins (RPs), which play a central role in the decoding of genetic code for the synthesis of new proteins. Over the past 25 years, studies on yeast and human models have made it possible to identify RPL10 (ribosomal protein L10), which is a constituent of the large subunit of the ribosome, as an important player in the final stages of ribosome biogenesis and in ribosome function.
  • 818
  • 30 Nov 2020
Topic Review
Ribosomal Gene Loci
Nucleoli form around actively transcribed ribosomal RNA (rRNA) genes (rDNA), and the morphology and location of nucleolus-associated genomic domains (NADs) are linked to the RNA Polymerase I (Pol I) transcription status. The number of rDNA repeats (and the proportion of actively transcribed rRNA genes) is variable between cell types, individuals and disease state. Substantial changes in nucleolar morphology and size accompanied by concomitant changes in the Pol I transcription rate have long been documented during normal cell cycle progression, development and malignant transformation. 
  • 646
  • 29 Jul 2021
Topic Review
Rho GTPase Regulators
The Rho family GTPases are small G proteins that act as molecular switches shuttling between active and inactive forms. Rho GTPases are regulated by two classes of regulatory proteins, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Rho GTPases transduce the upstream signals to downstream effectors, thus regulating diverse cellular processes, such as growth, migration, adhesion, and differentiation. In particular, Rho GTPases play essential roles in regulating neuronal morphology and function. Recent evidence suggests that dysfunction of Rho GTPase signaling contributes substantially to the pathogenesis of autism spectrum disorder (ASD). It has been found that 20 genes encoding Rho GTPase regulators and effectors are listed as ASD risk genes by Simons foundation autism research initiative (SFARI).
  • 428
  • 02 Jun 2021
Topic Review
Retinoic Acid
The retinoids are a group of compounds including vitamin A and its active metabolite all-trans-retinoic acid (ATRA). Retinoids regulate a variety of physiological functions in multiple organ systems, are essential for normal immune competence, and are involved in the regulation of cell growth and differentiation. Vitamin A derivatives have held promise in cancer treatment and ATRA is used in differentiation therapy of acute promyelocytic leukemia (APL). ATRA and other retinoids have also been successfully applied in a variety of dermatological conditions such as skin cancer, psoriasis, acne, and ichthyosis. Moreover, modulation of retinoic acid receptors and retinoid X (or rexinoid) receptors function may affect dermal cells. The studies using complex genetic models with various combinations of retinoic acid receptors (RARs) and retinoid X (or rexinoid) receptors (RXRs) indicate that retinoic acid and its derivatives have therapeutic potential for a variety of serious dermatological disorders including some malignant conditions.
  • 1.3K
  • 28 Dec 2020
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