Central Dogma, Selfish DNA and Noncoding RNAs: A Historical Perspective

Abstract

Major discoveries like the one gene-one enzyme hypothesis, demonstration of DNA as the genetic material and finally the elucidation of the double helical structure of DNA in 1940s and early 1950s set the stage for emergence of molecular biology. Parallel cell biological studies during this period also indicated a correlation between rate of protein synthesis in a cell and the amount of cytoplasmic RNA. Following the proposal of George Gamow, a physicist, about the triplet genetic code and possible involvement of RNA in the transfer of information from DNA to proteins, Crick proposed the 'central dogma of molecular biology' to suggest the paths of information transfer between nucleic acids and proteins, with the limitation that the information cannot flow back from protein to nucleic acids. With emphasis on proteins as the central phenotypic determinants and the continuing enigma of heterochromatin, which largely appeared to be 'gene desert', enriched in repetitive DNA sequences and claimed to be inert in transcription, the many observations in 1960s of a large variety of heterogeneous nuclear RNAs remained ignored. Curiosity in the nuclear RNAs that do not see the face of cytoplasm appeared to be quelled by concepts of 'selfish' or 'junk' DNA in the early 1980s, notwithstanding the fact that active transcription of typical constitutive heterochromatin regions and repetitive and other noncoding DNA sequences was well demonstrated in 1960s and 1970s. With a few exceptions like the hsrω and roX transcripts in Drosophila and the Xist RNAs in mammals, the noncoding RNAs remained largely ignored for nearly two decades. The discovery of RNA interference and sequencing of different eukaryotic genomes, including the human genome, led to revisits to possible significance of noncoding RNAs (ncRNAs) in the new millennium. The occasional identification of ncRNAs in early 2000s has in recent years transformed into a 'tsunami', resulting in concepts of 'selfish' or 'junk' DNA themselves becoming junk. There is now increasing realization that the subtle and large phenotypic effects of heterochromatin and the existence of diverse nucleus-limited RNAs reported through painstaking genetic and biochemical studies that were undertaken before molecular biology had grown fully, can be largely related to the enormous diversity of short and long ncRNAs now known to be produced by all genomes. Although Crick's proposal of Central Dogma was only about the directions of information transfer, its misinterpretation due to the great emphasis on the central roles of proteins and the reductionist linear approach of molecular biology that led to widespread belief in concepts of 'selfish' or 'junk' DNA, delayed the appreciation of multi-dimensional roles that ncRNAs actually play in maintaining homeostasis in complex biological networks.

Molecular regulation of hypoxia through the lenses of noncoding RNAs and epitranscriptome

“…Therefore, a substantial population of RNAs remains as noncoding RNAs (Abascal et al, 2020). Previously these noncoding RNAs were considered as transcriptional noise but eventually, several reports have shown that they have significant roles in various processes like pre-rRNA transcription, processing, and maturation (Lakhotia, 2018;Yan et al, 2019), regulation of chromosomal architecture and chromatin remodeling (Yao et al, 2019). Noncoding F I G U R E 1 Molecular regulation of hypoxic responsive genes under both normoxic and hypoxic conditions.…”

Transposons-Based Clonal Diversity in Trematode Involves Parts of CR1 (LINE) in Eu- and Heterochromatin

“…Heterochromatin variability could indicate the polymorphism rates in parthenogenetic clonal populations. There is a growing understanding that heterochromatin rearrangement and its tethering can be related to subtle and substantial phenotypic effects [65,66]. The identification of CR1-rng (LINE) in heterochromatin could provide insight into the mechanism of heterochromatin block variability.…”

Strategies against Nonsense: Oxadiazoles as Translational Readthrough-Inducing Drugs (TRIDs)

“…Protein synthesis is a crucial phase for any living organism; therefore, any phenomenon affecting any of the steps involved in such a crucial process could jeopardize life itself or cause severe disorders. Protein synthesis, in the classical vision of the central dogma, consists of two steps: transcription and translation (Figure 1) [1,2,3]. Therefore, any strategy aiming at correcting miscarried protein syntheses should intervene before the synthetic process is completed.…”