Transfer RNAs have been extensively explored as the molecules that translate the genetic code into proteins. At this interface of genetics and biochemistry, tRNAs direct the efficiency of every major step of translation by interacting with a multitude of binding partners. However, due to the variability of tRNA sequences and the abundance of diverse post-transcriptional modifications, a guidebook linking tRNA sequences to specific translational outcomes has yet to be elucidated. Here, we review substantial efforts that have collectively uncovered tRNA engineering principles that can be used as a guide for the tuning of translation fidelity. These principles have allowed for the development of basic research, expansion of the genetic code with non-canonical amino acids, and tRNA therapeutics.
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http://dx.doi.org/10.3389/fgene.2024.1436860 | DOI Listing |
Clin Epigenetics
December 2024
Hereditary Cancer Group, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain.
Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Computer Science, University of Haifa, Haifa 3303221, Israel.
Selective pressure acts on the codon use, optimizing multiple, overlapping signals that are only partially understood. We trained AI models to predict codons given their amino acid sequence in the eukaryotes and and the bacteria and to study the extent to which we can learn patterns in naturally occurring codons to improve predictions. We trained our models on a subset of the proteins and evaluated their predictions on large, separate sets of proteins of varying lengths and expression levels.
View Article and Find Full Text PDFAppl Health Econ Health Policy
December 2024
Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada.
Background: Patients with suspected rare diseases often experience lengthy and uncertain diagnostic pathways. This study aimed to estimate the cost-effectiveness of exome sequencing (ES) in different positions in the diagnostic pathway for patients suspected of having a rare genetic disease.
Methods: Data collected retrospectively from 305 patients suspected of having a rare genetic disease (RGD), who received clinical-grade ES and participated in the Canadian multicentre Care4Rare-SOLVE study, informed a discrete event simulation of the diagnostic pathway.
Reprod Sci
December 2024
Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
The advancement of next-generation sequencing has spurred the growing adoption of whole-exome sequencing (WES) for genetic screening. Preimplantation genetic testing for monogenic disorders (PGT-M) can effectively prevent the transmission of pathogenic variants. However, interpreting vast data volumes and ensuring precise genetic counseling, especially with variants of uncertain significance (VUS), remains challenging.
View Article and Find Full Text PDFMol Biol Rep
December 2024
Laboratório de Biologia Molecular (LBM), Centro de Bionegócios da Amazônia (CBA), Manaus, Amazonas, Brazil.
Background: Native to the Amazon region, Copaifera multijuga Hayne is a large tree (≈ 36 m in height) that is heavily exploited for extraction of its oleoresin. Many studies have addressed the phytochemical properties and applications of this raw material; however, there are few initiatives that have focused on the genetic characterization of native populations of this species. To this end, our objective was to develop microsatellite markers for C.
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