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Eser, Philipp; Wachutka, Leonhard; Maier, Kerstin C.; Demel, Carina; Boroni, Mariana; Iyer, Srignanakshi; Cramer, Patrick and Gagneur, Julien (2016): Determinants of RNA metabolism in the Schizosaccharomyces pombe genome. In: Molecular Systems Biology, Vol. 12, No. 2, 857 [PDF, 1MB]

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To decrypt the regulatory code of the genome, sequence elements must be defined that determine the kinetics of RNA metabolism and thus gene expression. Here, we attempt such decryption in an eukaryotic model organism, the fission yeast S. pombe. We first derive an improved genome annotation that redefines borders of 36% of expressed mRNAs and adds 487 non-coding RNAs (ncRNAs). We then combine RNA labeling invivo with mathematical modeling to obtain rates of RNA synthesis and degradation for 5,484 expressed RNAs and splicing rates for4,958 introns. We identify functional sequence elements inDNA and RNA that control RNA metabolic rates and quantifythecontributions of individual nucleotides to RNA synthesis,splicing, and degradation. Our approach reveals distinct kineticsof mRNA and ncRNA metabolism, separates antisense regulation by transcription interference from RNA interference, and provides a general tool for studying the regulatory code of genomes.

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