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PLoS One. 2016 Jan 22;11(1):e0143235. doi: 10.1371/journal.pone.0143235. eCollection 2016.

Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation.

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Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos, 138648, Singapore, Singapore.
Bioinformatics Institute, A*STAR, 30 Biopolis Street, 138671, Singapore, Singapore.
Life Technologies, 10 Biopolis Road, 138670, Singapore, Singapore.
Monash Bioinformatics Platform, Monash University, Clayton, Victoria, Australia.
EMBL-Australia Collaborating Group, Department of Genome Science, The John Curtin School of Medical Research (JCSMR), The Australian National University, Acton (Canberra), Australian Capital Territory, Australia.
Victor Chang Cardiac Research Institute, Darlinghurst (Sydney), New South Wales, Australia.
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore, Singapore.


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.

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