title: Impact of template backbone heterogeneity on RNA polymerase II transcription.
abstract: Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3'-5' or 2'-5' orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary 'imperfect' DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA.
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California San Diego, La Jolla, CA 92093-0625, USA.
authors: Liang
authors: L
authors: Xu
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California San Diego, La Jolla, CA 92093-0625, USA.
authors: Wei
authors: W
authors: Wang
authors: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors: Lu
authors: L
authors: Zhang
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California San Diego, La Jolla, CA 92093-0625, USA.
authors: Jenny
authors: J
authors: Chong
authors: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors: Xuhui
authors: X
authors: Huang
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California San Diego, La Jolla, CA 92093-0625, USA dongwang@ucsd.edu.
authors: Dong
authors: D
authors: Wang
mesh_terms: D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009711:Nucleotides / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D013698:Templates, Genetic; D014158:Transcription, Genetic
chemical_list: D009711:Nucleotides; D004247:DNA; D012319:RNA Polymerase II