Wen Jiang, Zhanyong Guo, Nuno Lages, W. Jim Zheng, Denis Feliers, Fangyuan Zhang, and Degeng Wang

SCIENCE REPORT Published online 2018 Apr 10. doi:  10.1038/s41598-018-24039-1

Abstract

To understand cellular coordination of multiple transcriptome regulation mechanisms, we simultaneously measured transcription rate (TR), mRNA abundance (RA) and translation activity (TA). This revealed multiple insights. First, the three parameters displayed systematic statistical differences. Sequentially more genes exhibited extreme (low or high) expression values from TR to RA, and then to TA; that is, cellular coordination of multiple transcriptome regulatory mechanisms leads to sequentially enhanced gene expression selectivity as the genetic information flow from the genome to the proteome. Second, contribution of the stabilization-by-translation regulatory mechanism to the cellular coordination process was assessed. The data enabled an estimation of mRNA stability, revealing a moderate but significant positive correlation between mRNA stability and translation activity. Third, the proportion of mRNA occupied by un-translated regions (UTR) exhibited a negative relationship with the level of this correlation, and was thus a major determinant of the mode of regulation of the mRNA. High-UTR-proportion mRNAs tend to defy the stabilization-by-translation regulatory mechanism, staying out of the polysome but remaining stable; mRNAs with little UTRs largely followed this regulation. In summary, we quantitatively delineated the relationship among multiple transcriptome regulation parameters, i.e., cellular coordination of corresponding regulatory mechanisms.

See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893539/

Figure 1: Experimental strategy. Log-phase HCT116 cells were split up into three parts. One part was used to extract total mRNA for RNA-seq analysis to measure steady-state mRNA abundance (RA) (black texts and arrows). One part was used to perform nuclear run-on to generate bromo-UTP labeled nascent RNA for sequencing, that is, GRO-seq analysis to measure transcription rate (TR) (red texts and arrows). The last part was used to isolate and quantify polysome associated mRNA to measure translation activity (TA) (green texts and arrows).