17 papers · ranked by Valyu relevance
Jie Wu, Cristian Eggers, Olga Sin, Łukasz Koziej + 10 more
Transfer RNA (tRNA) modifications tune translation rates and codon optimality, thereby optimizing co-translational protein folding. However, the mechanisms by which tRNA modifications modulate codon optimality and trigger phenotypes remain unclear. Here, we show that ribosomes stall at specific modification-dependent…
Sofia Radrizzani, Juan Rivas-Santisteban, Namshik Han, Laurence D. Hurst + 1 more
Despite early assumptions of neutrality, numerous mechanisms are now thought to cause selection on synonymous mutations, commonly supported by a low evolutionary rate at synonymous sites (Ks). This has been best evidenced in the first ~10 codons of genes in E. coli, where Ks is less than around half that of the gene…
Ruichu Gu, Duanmiao Si, Dingwei Lei, Xiaoxue Xie + 2 more
mRNA medicine is an emerging therapeutic approach that utilizes messenger RNA to synthesize functional proteins directly within target cells. This technology offers notable advantages including rapid development cycles, diverse therapeutic applications, and adaptable platform design for various diseases. However, mRNA…
Reed S. Sorenson, Leslie E. Sieburth
Degeneracy in the genetic code has been shown to play a major role in yeast mRNA stability; differences in optimality (charged tRNA supply vs demand) among synonymous codons were revealed as a determinant of mRNA decay rates. However, whether and how much this mechanism determines mRNA decay rates in plants is…
Mahua Bhattacharya, Aviad Sivan, Gideon Baum, Sumit Mukherjee + 1 more
The expression and functions of genes are largely dependent on genome integrity and stability. Codon usage plays a significant role in maintaining stability and functions of genes. Perturbation in codon sequence can lead to functional and structural dysfunction of a gene. In our study, we performed the codon usage…
Krisztina Kerekes, Mária Trexler, László Bányai, László Patthy
Somatic mutations drive carcinogenesis and aging, shortening the lifespan of animals. Since the vulnerability of genes strongly depends on their size and the abundance of mutation hotspots, we have tested whether negative selection of hypermutable (e.g., CpG bearing) codons could play a role in the evolution of…
Tapan Kumar Mohanta
Codon usage bias is a fundamental genomic characteristic that prefers non-random preferential use of synonymous codons. It is a major determinant of translational efficiency, gene regulation, and molecular evolution. However, the evolutionary bias and functional relevance of codon usage bias across the plant lineage is…
Seo, Yudam, Tlusty, Tsvi + 2 more
The origin and organizing principles of the genetic code remain fundamental puzzles in life science. The vanishingly low probability of the natural codon-to-amino acid mapping arising by chance has spurred the hypothesis that its structure is a solution optimized for robustness against mutations and translational…
Yoonho Jeong, Hyunwoo Choi, Ryan Fernandez Medina Hariri, Eok Kyun Lee + 2 more
Codon harmonization aims to adapt the coding sequences for heterologous expression while preserving the native-like patterns of frequent and rare codons that may influence local translation dynamics and co-translational protein folding. However, widely used harmonization metrics, such as $\%$MinMax, are defined on…
Juseong Kim, Jeongmu Kim, Jae-Wook Lee, Qian Qi + 4 more
Following the success of COVID-19 vaccines and therapies, mRNA-based therapeutics have attracted significant attention. Codon optimization is crucial for improving translation efficiency and mRNA stability, both of which are necessary for developing effective mRNA vaccines and drugs. Traditional approaches often rely…
Yudam Seo, Tsvi Tlusty, Junghyo Jo, Marc Robinson-Rechavi
The origin and organizing principles of the genetic code remain central problems in molecular evolution. The low probability of the natural codon-to-amino acid mapping arising by chance has spurred the hypothesis that its structure is optimized for robustness to mutations and translational errors. For the construction…
Thanyaporn Sirihongthong, Prasert Auewarakul
Codon usage pattern is a specific characteristic of each species as a result of evolution and interaction between genome composition and translational machinery. Species-specific optimal codon usage is a requirement for efficient expression in cells of that species. Viruses pose a curious situation where their genomes…
Andraz Jelincic, Ross C. Walker
The growing energy demand for computation is becoming increasingly unsustainable. Thermodynamic computing, which harnesses physical thermal fluctuations as a computational resource rather than suppressing them, offers orders-of-magnitude energy savings for probabilistic and combinatorial tasks. Pharmaceutical R&D…
Max Ward, Mary Richardson, Haining Lin, Michael Stamm + 7 more
mRNA medicines hold great promise, but designing sequences with high translation efficiency, robust in-solution stability, and manufacturability remains a major challenge due to the vast combinatorial space of synonymous coding sequences. Computational approaches such as mRNA folding algorithms have emerged as powerful…
Dhawa Sang Dong, Mausam Gurung, Suraj Kandel
Messenger RNA (mRNA) sequences as therapeutics require optimized design to ensure efficient translation, structural stability, and minimal immunogenicity. This study presents a two-stage in-silico framework that integrates deep learning and evolutionary computation for rational mRNA optimization instead of existing…
Mark Fornace, Christina Wuyan Wang, Michael Lindsey
Nucleic acid sequence design via codon optimization is a fundamental task with applications across synthetic biology, mRNA therapeutics, and vaccine design. Given a target protein, it is a major open challenge to navigate the combinatorially large design space of codon sequences mapping to its amino acid sequence.…
Jacques H. Daniel
Background/ Objectives: Resolving the origin of the genetic code is fundamental to understanding how life began its journey out of the chemical world. Since its deciphering some 60 years ago, there is still no general theory of the emergence of the genetic code. My objectives are to bring some unique data that might…