The Cell and Cell Division
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
RNA forms a single chain, whereas DNA forms a double helix held together by hydrogen bonding between bases on opposing strands; the individual nucleotides are held together by phosphate linkages between sugar residues (Fig. 24), the individual bases being suspended from the other end of the sugar residue. The sequence of bases forms the basis for all genetic information and is organized as a series of triplets, which code for individual amino acids. The hydrogen bonding between bases on opposing strands is not random, and on opposite sides of DNA, the following bases are always matched as complementary pairs (or Watson-Crick base pairs): G with CA with T (or A with U in RNA)
Neuropathogenesis of viral infections
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Interferons (IFN) are a group of proteins that derive their name from their ability to interfere with viral replication in an indirect fashion. There are three major families of interferons: IFN-α, IFN-β, and IFN-γ. IFN-α and IFN-β have potent antiviral properties within cells exposed to them, whereas IFN-γ enhances the immune system’s ability to clear infected cells mainly after the induction of the adaptive immune response. Therefore, expression of IFN-α and IFN-β early in the course of infection is crucial to preventing the further spread of the virus. IFN-α and IFN-β may become expressed by the presence of a variety of intracellular inducers, including the presence of foreign nucleic acids. In fact, the presence of double-stranded RNA is a potent inducer of their expression. IFN-γ is also important in controlling viral infection even in the absence of other cell mediated immune responses. For example, in measles virus infection, it can clear the virus from infected neurons without causing neuronal cell loss [29]. However, IFN-γ may also inhibit the proliferation of neural progenitor cells and thus affect brain repair and development [30].
Evolution
Paul Pumpens in Single-Stranded RNA Phages, 2020
However, the projects to reconstruct the cellular system from a set of defined molecules were endangered by the formation of double-stranded RNAs. To resolve the double-stranded RNA problems, Usui et al. (2013) elaborated the first kinetic model of the double-stranded RNA formation during replication of long RNAs by the Qβ replicase. Besides the genomic Qβ RNA, the two recombinant derivatives of the MDV-1 vector were used in this study: one carrying the β subunit encoding sequence and other encoding the β subunit and a part of the Qβ readthrough protein, 2125 and 3035 nucleotides in length, respectively. The authors showed that it was possible to suppress the double-stranded RNA formation by modification of the RNA sequence. Thus, they showed that the dsRNA formation could be explained quantitatively by two distinct pathways, i.e., (i) dsRNA formation during the replication process and (ii) dsRNA formation by hybridization through collision between the newly synthesized negative-strand RNA and positive-strand RNAs. Nevertheless, the levels of dsRNA formation by both reactions were reduced substantially by insertion of the readthrough part of the Qβ genome (Usui et al. 2013).
COVID-19: a wreak havoc across the globe
Published in Archives of Physiology and Biochemistry, 2023
Heena Rehman, Md Iftekhar Ahmad
There are two types of RNA which are synthesised by the virus, namely genomic and subgenomic RNAs. The sub-genomic RNAs act as mRNA for the structural and accessory genes. These genes are present downstream of the replicase polyprotein. The genomic and subgenomic RNAs are produced from negative RNA strand intermediate. There are certain cis-acting sequences which play a significant role in the replication of RNA. One of the cis-acting sequences is present within the 5′ UTR region. A seven looped structure is present in 5′ UTR region, which may stretch into replicase 1a (Raman et al. 2003, Brown et al. 2007, Liu et al. 2009, Guan et al. 2011). Another cis-acting sequence is present in the 3′ UTR region which is a bulged stem-loop, hypervariable region and a pseudoknot (Hsue and Masters 1997, Williams et al. 1999, Liu et al. 2001, Goebel et al. 2007). However, the stem loop structure and pseudoknot in the 3′ UTR region overlap each other; hence, they cannot form together (Hsue and Masters 1997, Williams et al. 1999, Hsue et al.2000, Goebel et al. 2007). All of these structures control alternate phases of synthesis of RNA. During the production of subgenomic RNAs, the body TRS and leader sequences fuse together. It is speculated that it occurs during the synthesis of positive strand of RNA (Sawicki et al. 2007). RNA dependent RNA polymerase (RdRp) halts at any of the TRS sequence. After this halt, the RdRp either continues elongation to next TRS or switches to multiply leader sequence at 5′ endguided by complementarity of TRS to leader TRS.
Efficacy of siRNA-loaded nanoparticles in the treatment of K-RAS mutant lung cancer in vitro
Published in Journal of Microencapsulation, 2022
Ayse Gencer, Ipek Baysal, Emirhan Nemutlu, Samiye Yabanoglu-Ciftci, Betul Arica
The mechanism of the cancer formation is directly or indirectly related to genetic mutations and activation of oncogenes (Heng et al.2010). Gene therapy involves strategies such as repairing, suppressing, or silencing genes that cause cancer formation. The advantage of gene therapy over other treatment approaches is that it is highly specific and suitable for developing individual treatment strategies (Cross and Burmester 2006, Amer 2014). RNA interference is one of the most important genes therapy techniques. It effects through a pathway where double-stranded RNA is attached to the target mRNA of the gene to be silenced and degrades thus, preventing the synthesis of the protein associated with cancer after transcription. For this purpose, small interfering RNA (siRNA) molecules of 20–25 nucleotides length, are obtained by breaking down double stranded RNA (dsRNA) into small RNA fragments by the Dicer enzyme (an RNase III endonuclease which is involved in the biogenesis of small RNAs) are used (Song and Rossi 2017). After the transfection of siRNA into cells via different transfection methods, it forms a complex with RNA-Induced Silencing Complex (RISC) containing endonuclease, exonuclease, and helicase enzymes in its structure. This complex binds to target mRNA by recognise it through the siRNA. As a result, the mRNA is degraded and inactivated by RISC (Devi 2006, Rao et al.2013, Mansoori et al.2014).
Targeting the TGF-β signaling pathway for fibrosis therapy: a patent review (2015–2020)
Published in Expert Opinion on Therapeutic Patents, 2021
Xuanyi Li, Ziang Ding, Zixuan Wu, Yinqiu Xu, Hequan Yao, Kejiang Lin
RNA interference is a process of effectively silencing specific genes. The silencing mechanism can induce the degradation of targeted mRNA by siRNA or shRNA or inhibit the translation process of mRNA through miRNA. Jia et al. from Xuanwu Hospital of Capital Medical University chose an shRNA targeting TGF-β1 to degrade mRNA and reduce expression of TGF-β1 at the mRNA level [62]. Matsumoto et al. from Bonac Corp. used novel single-stranded nucleic acid molecules, including single-stranded RNA oligomers linked by L-proline diamine amide linker (LX), which replaced siRNA to target TGF-β1. Single-stranded nuclear acid molecules were described in detail in both WO2015093495 and WO2016098782, and the former has entered stage I clinical practice [63,64]. Since then, Yamada et al. of Bonac Corp. used the above structure to design a single-stranded nucleic acid molecule to inhibit TGF-β1 mRNA [65]. Zhou et al. from Sirnaomics, Inc. used histidine-lysine copolymer (HKP) to deliver siRNA targeting TGF-β1 and COX-2 genes to achieve gene silencing and activate apoptosis in fibroblasts and myofibroblasts [66]. Zhang et al. from Sirnaomics, Inc. modified siRNA targeting TGF-β1, and combined a trivalent-GalNAc conjugate, bivalent-GalNAc conjugate and monovalent-GalNAc conjugate as ligands in the sense chain to realize siRNA targeting in vivo [67].