PT  - JOURNAL ARTICLE
AU  - Philipp Eser
AU  - Leonhard Wachutka
AU  - Kerstin C. Maier
AU  - Carina Demel
AU  - Mariana Boroni
AU  - Srignanakshi Iyer
AU  - Patrick Cramer
AU  - Julien Gagneur
TI  - Determinants of RNA metabolism in the <em>Schizosaccharomyces pombe</em> genome
AID  - 10.1101/025585
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 025585
4099  - http://biorxiv.org/content/early/2015/08/26/025585.short
4100  - http://biorxiv.org/content/early/2015/08/26/025585.full
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.