The RNA–Protein World

Altman, Sidney

doi:10.1261/rna.038687.113

Cited by 19 publications

(11 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ribosome-first theory is the only current theory that is consistent with all data gathered here and the only one that explains the co-evolution of genetic information and translation function from the outset. The ribosome first theory is consistent with the prebiotic evolution of an RNA–protein world [12,146,147,148,149,150], thereby integrating observations that both RNA species (“RNA world” scenarios [11,150,151,152,153,154,155,156]) and amino acids (“protein world” scenarios [157,158]) were present simultaneously from the outset. More importantly, the ribosome-first theory is consistent with multiple taxonomic studies that all place the origin of functional ribosomes earlier than the last universal common ancestor (LUCA) and therefore, with high probability, prior to the inception of cellular life itself [159,160,161,162,163].…”

Section: Discussionmentioning

confidence: 87%

The Ribosome as a Missing Link in Prebiotic Evolution III: Over-Representation of tRNA- and rRNA-Like Sequences and Plieofunctionality of Ribosome-Related Molecules Argues for the Evolution of Primitive Genomes from Ribosomal RNA Modules

Root‐Bernstein

2019

IJMS

View full text Add to dashboard Cite

We propose that ribosomal RNA (rRNA) formed the basis of the first cellular genomes, and provide evidence from a review of relevant literature and proteonomic tests. We have proposed previously that the ribosome may represent the vestige of the first self-replicating entity in which rRNAs also functioned as genes that were transcribed into functional messenger RNAs (mRNAs) encoding ribosomal proteins. rRNAs also encoded polymerases to replicate itself and a full complement of the transfer RNAs (tRNAs) required to translate its genes. We explore here a further prediction of our “ribosome-first” theory: the ribosomal genome provided the basis for the first cellular genomes. Modern genomes should therefore contain an unexpectedly large percentage of tRNA- and rRNA-like modules derived from both sense and antisense reading frames, and these should encode non-ribosomal proteins, as well as ribosomal ones with key cell functions. Ribosomal proteins should also have been co-opted by cellular evolution to play extra-ribosomal functions. We review existing literature supporting these predictions. We provide additional, new data demonstrating that rRNA-like sequences occur at significantly higher frequencies than predicted on the basis of mRNA duplications or randomized RNA sequences. These data support our “ribosome-first” theory of cellular evolution.

show abstract

Section: Discussionmentioning

confidence: 87%

The Ribosome as a Missing Link in Prebiotic Evolution III: Over-Representation of tRNA- and rRNA-Like Sequences and Plieofunctionality of Ribosome-Related Molecules Argues for the Evolution of Primitive Genomes from Ribosomal RNA Modules

Root‐Bernstein

2019

IJMS

View full text Add to dashboard Cite

show abstract

“…8 ). This is particularly interesting considering that we are still in an RNA–protein world rather than a completely protein world 39 40 41 .…”

Section: Discussionmentioning

confidence: 99%

Specificity and catalysis hardwired at the RNA–protein interface in a translational proofreading enzyme

et al. 2015

View full text Add to dashboard Cite

Proofreading modules of aminoacyl-tRNA synthetases are responsible for enforcing a high fidelity during translation of the genetic code. They use strategically positioned side chains for specifically targeting incorrect aminoacyl-tRNAs. Here, we show that a unique proofreading module possessing a D-aminoacyl-tRNA deacylase fold does not use side chains for imparting specificity or for catalysis, the two hallmark activities of enzymes. We show, using three distinct archaea, that a side-chain-stripped recognition site is fully capable of solving a subtle discrimination problem. While biochemical probing establishes that RNA plays the catalytic role, mechanistic insights from multiple high-resolution snapshots reveal that differential remodelling of the catalytic core at the RNA–peptide interface provides the determinants for correct proofreading activity. The functional crosstalk between RNA and protein elucidated here suggests how primordial enzyme functions could have emerged on RNA–peptide scaffolds before recruitment of specific side chains.

show abstract

“…The understanding of the role of RNA in cell biology underwent a sea change in the early 1980s, when RNA moved from being perceived as a passive player in the transfer of information between DNA and protein synthesis to playing significant structural, enzymatic and information‐decoding roles during protein synthesis. Walter Gilbert first proposed the concept of ‘The RNA World’ in 1986 and the pathway of RNA interference [RNAi] was discovered by Fire et al and colleagues in the nematode Caenorhabditis elegans in 1998 . The natural function of RNAi appears to be protection of the genome against invasion by mobile genetic material such as from viruses that produce aberrant RNA or dsRNA when they become active and thus RNA interference serves as a powerful defence mechanism.…”

Section: Rna Therapeuticsmentioning

confidence: 99%

Therapeutic nucleic acids: current clinical status

Sridharan

Gogtay

2016

Brit J Clinical Pharma

201

134

View full text Add to dashboard Cite

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are simple linear polymers that have been the subject of considerable research in the last two decades and have now moved into the realm of being stand-alone therapeutic agents. Much of this has stemmed from the appreciation that they carry out myriad functions that go beyond mere storage of genetic information and protein synthesis. Therapy with nucleic acids either uses unmodified DNA or RNA or closely related compounds. From both a development and regulatory perspective, they fall somewhere between small molecules and biologics. Several of these compounds are in clinical development and many have received regulatory approval for human use. This review addresses therapeutic uses of DNA based on antisense oligonucleotides, DNA aptamers and gene therapy; and therapeutic uses of RNA including micro RNAs, short interfering RNAs, ribozymes, RNA decoys and circular RNAs. With their specificity, functional diversity and limited toxicity, therapeutic nucleic acids hold enormous promise. However, challenges that need to be addressed include targeted delivery, mass production at low cost, sustaining efficacy and minimizing off-target toxicity. Technological developments will hold the key to this and help accelerate drug approvals in the years to come. IntroductionDeoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are simple linear polymers that consist of only four major subunits, yet these molecules carry out myriad functions both within the cell and in the laboratory [1]. Early assessment of nucleic acid function was rather narrow and restricted, but research in the past few decades has seen remarkable progress in developing nucleic acid-based therapeutics. The progress has covered diverse fields of research and a significant number of scientists and engineers are now involved in this area [2]. A series of pivotal discoveries in the last three decades has made this possible. First, a large body of work has obviously followed the decoding of the human genome that unlocked several molecular pathways that are important in disease. Secondly, several types of RNA with complex biological functions have been discovered in addition to messenger RNA (mRNA) and transfer RNA (tRNA) [1]. For example, two non-coding RNA types that were not considered essential but are now extremely relevant to therapeutics are the microRNA (miRNA) and the short interfering RNA (siRNA). Thirdly, the appreciation that RNAs can act as enzymes has led to the development of RNA analogues with useful or unusual properties. Of the analogues, the locked nucleic acids or LNAs have found therapeutic applications. In view of their polar nature, the cellular delivery of nucleic acids is poor relative to conventional low molecular weight drugs. The fourth major advance has been enhancing the bioavailability of nucleic acid-based drugs. None of these would have been possible without technological advances in DNA synthesis, including the de novo synthesis of increasingly longer DNA British Journal of Cli...

show abstract

The RNA–Protein World

Cited by 19 publications

References 12 publications

The Ribosome as a Missing Link in Prebiotic Evolution III: Over-Representation of tRNA- and rRNA-Like Sequences and Plieofunctionality of Ribosome-Related Molecules Argues for the Evolution of Primitive Genomes from Ribosomal RNA Modules

The Ribosome as a Missing Link in Prebiotic Evolution III: Over-Representation of tRNA- and rRNA-Like Sequences and Plieofunctionality of Ribosome-Related Molecules Argues for the Evolution of Primitive Genomes from Ribosomal RNA Modules

Specificity and catalysis hardwired at the RNA–protein interface in a translational proofreading enzyme

Therapeutic nucleic acids: current clinical status

Contact Info

Product

Resources

About