Going Beyond the Central Dogma of Molecular Biology: Rather than Being a One-Way Street, DNA-Directed RNA Transcription May Have Profound Adaptability

Using single cell transcriptogenomics to probe the cell’s defense mechanisms, study published in Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Amsterdam, March 11, 2015

The central dogma of molecular biology describes the flow of genetic information. It was first described by Francis Crick in 1956 as one-way traffic: as: "DNA makes RNA and RNA makes protein."

A recent paper published in Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, however suggests that, rather than being a one-way street, DNA-directed RNA transcription may have profound adaptability. The authors of the paper showed aconceptually novel relationship between the genotype (DNA) and the phenotype (the products of the transcription of DNA).

The method the authors used to make this discovery is termed Single-Cell Transcriptogenomics (SCTG). It allows DNA and RNA sequencing to be performed concurrently on the same single cells taken from a cell population treated with the powerful mutagen ethylnitrosourea. This method allowed the authors, for the first time, to prove the tendency of the transcriptional machinery in the cell to avoid transcribing DNA strands harboring a newly induced mutation. This is likely to be a novel cellular defense mechanism to prevent genetic mutations from being expressed.

“We described a novel method to directly examine the transcription pattern of genotypic variants at single cell resolution,” explained Dr. Jan Vijg, Department of Genetics, Albert Einstein College of Medicine, lead author of the paper. “Single-cell transcriptogenomics will be instrumental in gaining a more complete understanding of how variations in the genome can lead to functional deficiencies in aging and disease."


 Notes for editors
This paper is: “Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles” by Wenge Li, R. Brent Calder, Jessica C. Mar, Jan Vij (doi:10.1016/j.mrfmmm.2015.01.002), Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis published by Elsevier. The paper is published open access: http://www.sciencedirect.com/science/article/pii/S0027510715000044

About Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
The journal is a platform for publishing research papers covering aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. It publishes full-length research articles, short research communications, reviews and mini-reviews, letters to the editor, book reviews and meeting reports Read more here: www.journals.elsevier.com/mutation-research-fundamental-and-molecular-mechanisms-of-mutagenesis

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