Editorial: Synthetic biology and therapeutic applications of transfer RNA
Notice bibliographique
Résumé
Because of their central role in protein synthesis, engineered and synthetic tRNAs emerged as essential components of orthogonal translation systems that are designed to incorporate noncanonical or even unnatural amino acids into proteins in cells and cell-free systems. Furthermore, recent efforts have used either normal wild-type or engineered tRNAs to correct genetic defects that cause human disease. Since 11% of inherited human genetic diseases are caused by premature stop codons, nonsense suppressor tRNAs are of increasing interest for applications in tRNA therapeutics. We recognize that both synthetic biology and therapeutic applications of tRNAs will rely on nonsense and in some cases missense suppressor tRNAs, to generate novel proteins or to correct genetic defects. Thus, this Research Topic for Frontiers in Genetics features genetic code expansion and probing the role of tRNAs in translation for applications in synthetic biology and medicine.Several contributions in this special issue focus on the role and engineering of aminoacyl-tRNA synthetases and tRNAs in genetic code expansion. Research in this field has enabled the production of recombinant proteins with genetically encoded non-canonical amino acids, such as phosphoserine and N-acetyl-lysine. Jiang et al present an engineered pyrrolysyl-tRNA synthetase (PylRS), which, rather than its natural substrate pyrrolysine (Pyl), instead directly charges tRNA Pyl with a D-amino acid. Successful incorporation of D-phenylalanine analogs (DFAs) into both the superfolder green fluorescent protein and human heavy chain ferritin was demonstrated. Incorporation of D-amino acids is selected against in the endogenous translational machineries, where only L-amino acids are incorporated with high fidelity. The development of this newly evolved PylRS•tRNA Pyl pair will allow the site-directed incorporation of D-amino acids into a diverse array of recombinant proteins. Potential future application areas include using genetically programmed D-amino acids to generate optically active proteins for therapeutic applications or the evolution of novel protein functions that are inaccessible to normal cells.While significant progress has been made in engineering the aminoacyl-tRNA synthetases, such as PylRS, to expand the palebe of different proteinogenic amino acids, the engineering of tRNAs has only more recently come into focus as a major approach to optimize and tune nonsense and Their overall goal was to use sense codons rather than stop codons, to expand the genetic code with non-canonical amino acids. Anticodons with an adenosine in the wobble positions are often modified to inosine, allowing for expanded decoding of multiple codons allowing the I34containing tRNA to base pair with U, C, or A at the wobble position. Since this fact has important implications for the fidelity and specificity of sense codon reassignment, the authors evaluated the missense suppression efficiencies of 15 of the 16 possible orthogonal tRNAs with A34 anticodons and found that the I34 modification only occurred in a minority of the engineered
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».