title: Determinants of RNA metabolism in the Schizosaccharomyces pombe genome.
abstract: 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 in vivo with mathematical modeling to obtain rates of RNA synthesis and degradation for 5,484 expressed RNAs and splicing rates for 4,958 introns. We identify functional sequence elements in DNA and RNA that control RNA metabolic rates and quantify the contributions of individual nucleotides to RNA synthesis, splicing, and degradation. Our approach reveals distinct kinetics of 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.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Eser
authors.affiliation: Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Wachutka
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Kerstin C
authors.initials: KC
authors.lastname: Maier
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Demel
authors.affiliation: Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Mariana
authors.initials: M
authors.lastname: Boroni
authors.affiliation: Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Srignanakshi
authors.initials: S
authors.lastname: Iyer
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany patrick.cramer@mpibpc.mpg.de gagneur@in.tum.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
authors.affiliation: Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, Munich, Germany patrick.cramer@mpibpc.mpg.de gagneur@in.tum.de.
authors.forename: Julien
authors.initials: J
authors.lastname: Gagneur
mesh_terms: D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D007438:Introns; D034622:RNA Interference; D012326:RNA Splicing; D016372:RNA, Antisense / Q000235:genetics; D012331:RNA, Fungal / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
chemical_list: D016372:RNA, Antisense; D012331:RNA, Fungal; D012333:RNA, Messenger
keywords: RNA degradation; RNA synthesis; cis‐regulatory element; gene regulation; splicing