RT Journal Article SR Electronic T1 Determinants of RNA metabolism in the Schizosaccharomyces pombe genome JF bioRxiv FD Cold Spring Harbor Laboratory SP 025585 DO 10.1101/025585 A1 Philipp Eser A1 Leonhard Wachutka A1 Kerstin C. Maier A1 Carina Demel A1 Mariana Boroni A1 Srignanakshi Iyer A1 Patrick Cramer A1 Julien Gagneur YR 2015 UL http://biorxiv.org/content/early/2015/08/26/025585.abstract AB 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.