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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Ribozymes were discovered in the early 1980s by Thomas Cech and Sidney Altman, who shared the Nobel Prize in Chemistry for their discovery in 1989. They postulated that RNA in this form can act as both genetic material (like DNA) and as a biological catalyst (like protein enzymes) which contributed to the “RNA World Hypothesis” which proposes that RNA may have been important in the evolution of prebiotic self-replicating systems. Investigators studying the origin of life have produced ribozymes in the laboratory that are capable of catalyzing their own synthesis under specific conditions (i.e., having an RNA polymerase activity). These studies led to the suggestion that, in the past, cells used RNA as both genetic material and as structural and catalytic molecules, rather than dividing these functions between DNA and protein as they are today.
Evolution
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The history and progress of the scientific and practical applications of the molecular colonies was analyzed in detail by Chetverin and Chetverina (2007). In particular, they noticed that Mitra and Church (1999) published a PCR version of the molecular colony technique under the name of polony (polymerase colony) technology. Next, they noticed that Szostak (1999) was the first to indicate that molecular colonies, analogous to those formed when RNA was amplified in agarose with Qβ replicase, could have represented a precellular variant of compartmentalization in the RNA World. In this case, the compartmentalization was provided not by an envelope but by a relatively low diffusion rate of macromolecules in a porous matrix as compared with the diffusion rate of low molecular mass substances. According to Szostak, the RNA colonies could be formed in moist clay and other porous minerals (cited by Chetverin and Chetverina 2007). This idea was further developed by Alexander Spirin (2002, 2005a,b), who postulated that the mixed colonies comprising the following three species of macromolecules could be the first individuals in the RNA World: (i) ligand-binding RNA molecules for selective adsorption and accumulation of necessary substances from the environment; (ii) a set of ribozymes catalyzing the metabolic reactions of nucleotide synthesis; and (iii) a ribozyme catalyzing complementary replication of all RNA molecules of the colony.
Beyond Enzyme Kinetics
Published in Clive R. Bagshaw, Biomolecular Kinetics, 2017
Although nucleic acids and their interactions in vivo are usually associated with proteins in complex assemblies, there is much interest in the kinetics of intermolecular and intramolecular interactions of nucleic acids in isolation for two reasons. The melting and annealing of DNA strands are central to biotechnology and protocols reflect the need for near quantitative conversion of reactants to products in reactions that are controlled by both thermodynamics and kinetics. The importance of this aspect is well illustrated by optimization of the polymerase chain reaction, which includes both enzyme-catalyzed and -uncatalyzed steps. Second, RNA interactions are of interest in understanding evolution via the RNA world [204] and, more recently, in understanding the diverse role of noncoding RNA in the cellular control mechanisms [205,206].
First Report of the 3'-Untranslated Region +1506 (A>C) [NM_000518.5: c.*32A>C] mutation on the β-Globin Gene in the Indian Population
Published in Hemoglobin, 2021
Aditi Sen, Venu Seenappa, Prantar Chakrabarti, Tuphan Kanti Dolai
β-Thalassemia (β-thal) is a hereditary blood disorder characterized by anomalies on the β chain synthesis of hemoglobin (Hb) and displays a high level of molecular and clinical heterogeneity [1]. Variants such as point mutations, small indels and large deletions, are reported in the human β-globin gene affecting the expression and resulting in the clinical syndromes of β-thal minor, β-thal intermedia (β-TI) and β-thal major (β-TM) [2]. The outcome of these mutations is the inhibition of efficient β gene transcription and/or mRNA processing, resulting in decreased mRNA levels [3]. Although, the main regulation of gene expression was considered to occur at the transcriptional level, with major roles for transcription factor recruitment/activation at promoter elements, the post-transcriptional events are also equally reported in the β-globin gene regulation [4]. With progressive increase of knowledge about the RNA world, non coding mRNA regions are now known to play an additional unique role in the regulation of gene expression. In this context, a cis-acting regulatory sequence present in either 5′- or 3′-untranslated regions (5′- or 3′-UTRs) of the vast majority of genes recognized by trans-acting factors, and their interaction has shown a strong impact on the post-transcriptional regulation [4].