Accurate transcription is required for the faithful expression of genetic information. To understand the molecular mechanisms that control the fidelity of transcription, we used novel sequencing technology to provide the first comprehensive analysis of the fidelity of transcription in eukaryotic cells. Our results demonstrate that transcription errors can occur in any gene, at any location, and affect every aspect of protein structure and function. In addition, we show that multiple proteins safeguard the fidelity of transcription and provide evidence suggesting that errors that evade these layers of RNA quality control profoundly affect the physiology of living cells. Together, these observations demonstrate that there is an inherent limit to the faithful expression of the genome and suggest that the impact of mutagenesis on cellular health and fitness is substantially greater than currently appreciated.
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http://dx.doi.org/10.1126/sciadv.1701484 | DOI Listing |
Squamous cell carcinomas (SCC) are often preceded by potentially malignant precursor lesions, most of which remain benign. The terminal exhaustion phenotypes of effector T-cells and the accumulation of myeloid-derived suppressor cells (MDSC) have been thoroughly characterized in established SCC. However, it is unclear what precancerous lesions harbor a bona fide high risk for malignant transformation and how precancerous epithelial dysplasia drives the immune system to the point of no return.
View Article and Find Full Text PDFTrends Cell Biol
December 2024
Cologne Excellence Cluster for Aging and Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Electronic address:
Cellular homeostasis declines with age due to the declining fidelity of biosynthetic processes and the accumulation of molecular damage. Yet, it remains largely elusive how individual processes are affected during aging and what their specific contribution to age-related functional decline is. This review discusses a series of recent publications that has shown that transcription elongation is compromised during aging due to increasing DNA damage, stalling of RNA polymerase II (RNAPII), erroneous transcription initiation in gene bodies, and accelerated RNAPII elongation.
View Article and Find Full Text PDFAm J Hosp Palliat Care
December 2024
Penn State College of Medicine, Hershey, PA, USA.
Context: Health inequities in Hispanic populations require community-engaged solutions. Engaging Hispanic communities in research related to advance care planning (ACP) is critical to inform the development and evaluation of culturally appropriate interventions.
Objectives: To understand how to best adapt and implement Spanish-language ACP interventions in Hispanic communities across the US.
The ability of cancer cells to alter their identity, known as lineage plasticity, is crucial for tumor progression and therapy resistance. In lung adenocarcinoma (LUAD), tumor progression is characterized by a gradual loss of lineage fidelity and the emergence of non-pulmonary identity programs. This can lead to hybrid-identity (hybrid-ID) states in which developmentally incompatible identity programs are co-activated within individual cells.
View Article and Find Full Text PDFGene knockout strain collections are important tools for discovery in microbiology. The only available genome-wide deletion collection for a human pathogenic fungus, is utilized widely for genetic studies. We uncovered mix-ups in the assembly of the commercially available deletion collection of ∼6,000 unique strains acquired by our lab.
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