Wong QW-L, Vaz C, Lee QY, Zhao TY, Luo R, Archer SK, et al. (2016) Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation. PLoS ONE 11(1): e0143235. doi:10.1371/journal.pone.0143235
Abstract:
The presence of multiple variants for many mRNAs is a major contributor to protein diversity. The processing of these variants is tightly controlled in a cell-type specific manner and has a significant impact on gene expression control. Here we investigate the differential translation rates of individual mRNA variants in embryonic stem cells (ESCs) and in ESC derived Neural Precursor Cells (NPCs) using polysome profiling coupled to RNA sequencing. We show that there are a significant number of detectable mRNA variants in ESCs and NPCs and that many of them show variant specific translation rates. This is correlated with
differences in the UTRs of the variants with the 5’UTR playing a predominant role. We suggest that mRNA variants that contain alternate UTRs are under different post-transcriptional controls. This is likely due to the presence or absence of miRNA and protein binding sites that regulate translation rate. This highlights the importance of addressing translation rate when using mRNA levels as a read out of protein abundance. Additional analysis shows that many annotated non-coding mRNAs are present on the polysome fractions in ESCs and NPCs. We believe that the use of polysome fractionation coupled to RNA sequencing is a useful method for analysis of the translation state of many different RNAs in the cell.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
QWLW, CV, QYL, TYZ, VTand LAV were funded by the Agency for Science, Technology and Research, Singapore. Raymond Luo, a co-author in this study, is employed by Life Technologies, 10 Biopolis Road, Singapore 138670. The funder provided support in the form of salaries for authors [RL], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. RL was involved in data analysis. The specific roles of the author is articulated in the ‘author contributions’ section. TP acknowledges funding from the Australian Research Council (grant DP1300101928).