Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation
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 indiv...
Main Authors: | , , , , , , , , |
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Format: | Journal Article |
Language: | English |
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2016
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Online Access: | https://hdl.handle.net/10356/82675 http://hdl.handle.net/10220/40226 |
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author | Wong, Queenie Wing-Lei Vaz, Candida Lee, Qian Yi Zhao, Tian Yun Luo, Raymond Archer, Stuart K. Preiss, Thomas Tanavde, Vivek Vardy, Leah Anne |
author2 | Jan, Eric |
author_facet | Jan, Eric Wong, Queenie Wing-Lei Vaz, Candida Lee, Qian Yi Zhao, Tian Yun Luo, Raymond Archer, Stuart K. Preiss, Thomas Tanavde, Vivek Vardy, Leah Anne |
author_sort | Wong, Queenie Wing-Lei |
collection | NTU |
description | 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. |
first_indexed | 2024-10-01T04:39:30Z |
format | Journal Article |
id | ntu-10356/82675 |
institution | Nanyang Technological University |
language | English |
last_indexed | 2024-10-01T04:39:30Z |
publishDate | 2016 |
record_format | dspace |
spelling | ntu-10356/826752023-02-28T16:58:39Z Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation Wong, Queenie Wing-Lei Vaz, Candida Lee, Qian Yi Zhao, Tian Yun Luo, Raymond Archer, Stuart K. Preiss, Thomas Tanavde, Vivek Vardy, Leah Anne Jan, Eric School of Biological Sciences NPC Neural Precursor Cell ESC Embryonic Stem Cell 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. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2016-03-08T07:03:52Z 2019-12-06T15:00:10Z 2016-03-08T07:03:52Z 2019-12-06T15:00:10Z 2016 Journal Article Wong, Q. W.-L., Vaz, C., Lee, Q. Y., Zhao, T. Y., Luo, R., Archer, S. K., et al. (2016). Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation. PLoS ONE, 11(1), e0143235-. 1932-6203 https://hdl.handle.net/10356/82675 http://hdl.handle.net/10220/40226 10.1371/journal.pone.0143235 26799392 en PLoS ONE © 2016 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 19 p. application/pdf |
spellingShingle | NPC Neural Precursor Cell ESC Embryonic Stem Cell Wong, Queenie Wing-Lei Vaz, Candida Lee, Qian Yi Zhao, Tian Yun Luo, Raymond Archer, Stuart K. Preiss, Thomas Tanavde, Vivek Vardy, Leah Anne Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation |
title | Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation |
title_full | Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation |
title_fullStr | Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation |
title_full_unstemmed | Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation |
title_short | Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation |
title_sort | embryonic stem cells exhibit mrna isoform specific translational regulation |
topic | NPC Neural Precursor Cell ESC Embryonic Stem Cell |
url | https://hdl.handle.net/10356/82675 http://hdl.handle.net/10220/40226 |
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