PT  - JOURNAL ARTICLE
AU  - J. Feltham
AU  - S. Xi
AU  - S. Murray
AU  - M. Wouters
AU  - J. Urdiain-Arraiza
AU  - C. George
AU  - A. Townley
AU  - E. Roberts
AU  - R. Fisher
AU  - S. Liberatori
AU  - S. Mohammed
AU  - B. Kessler
AU  - J. Mellor
TI  - Transcriptional changes are regulated by metabolic pathway dynamics but decoupled from protein levels
AID  - 10.1101/833921
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 833921
4099  - http://biorxiv.org/content/early/2019/11/07/833921.short
4100  - http://biorxiv.org/content/early/2019/11/07/833921.full
AB  - The central dogma of molecular biology states that information flows from DNA to protein via RNA (Crick, 1970). This model is central to our understanding of biology but can lead to the assumption that changes in transcription and transcripts will inevitably lead to changes in protein levels, and so directly impact the metabolic and biosynthetic state of the cell. To test this assumption, we used a biological system characterised by genome-wide, cyclical changes in transcription, to assess whether changes in transcription are reflected in changes at the level of protein. We reveal that despite large changes in transcription at the majority of genes, there is little change in protein. This decoupling results from the slow rate of protein turnover. The changes protein activity we did observe were instead a reflection of the metabolic state of the cell, resulting from post-transcriptional modifications such as acetylation and phosphorylation, that in turn drive the cycling of processes such as transcription and ribosome biogenesis. Thus, transcriptional and transcript cycling reflects rather than drives the metabolic and biosynthetic changes during biological rhythms. We suggest that caution is needed when inferring the activity of biological processes from transcript data, as this reflects but does not predict a cell’s state.