Chromatin measurements reveal contributions of synthesis and decay to steady-state mRNA levels.
Messenger RNA levels in eukaryotes are controlled by multiple consecutive regulatory processes, which can be classified into two layers: primary transcriptional regulation at the chromosomal level and secondary, co- and post-transcriptional regulation of the mRNA. To identify the individual contribution of these layers to steady-state RNA levels requires separate quantification. Using mouse as a model organism, we show that chromatin features are sufficient to model RNA levels but with different sensitivities in dividing versus postmitotic cells. In both cases, chromatin-derived transcription rates explain over 80% of the observed variance in measured RNA levels. Further inclusion of measurements of mRNA half-life and microRNA expression data enabled the identification of a low quantitative contribution of RNA decay by either microRNA or general differential turnover to final mRNA levels. Together, this establishes a chromatin-based quantitative model for the contribution of transcriptional and post-transcriptional processes to steady-state levels of messenger RNA.
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Sylvia C
SC
Tippmann
Robert
R
Ivanek
Dimos
D
Gaidatzis
Anne
A
Schöler
Leslie
L
Hoerner
Erik
E
van Nimwegen
Peter F
PF
Stadler
Michael B
MB
Stadler
Dirk
D
Schübeler
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation / Q000379:methods; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods; D014158:Transcription, Genetic
D002843:Chromatin; D035683:MicroRNAs; D012333:RNA, Messenger; D018698:Glutamic Acid