Embryonic Stem Cells Exhibit MRNA Isoform Specific Translational Regulation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Jan 23

PMID 26799392

Citations 10

Authors

Queenie Wing-Lei Wong

Candida Vaz

Qian Yi Lee

Tian Yun Zhao

Raymond Luo

Stuart K Archer

Thomas Preiss

Vivek Tanavde

Leah A Vardy

Affiliations

Soon will be listed here.

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.

Citing Articles

The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.

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Translational and post-translational control of human naïve versus primed pluripotency.

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Translational control of stem cell function.

Saba J, Liakath-Ali K, Green R, Watt F Nat Rev Mol Cell Biol. 2021; 22(10):671-690.

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Insights Into Translatomics in the Nervous System.

Zhang S, Chen Y, Wang Y, Zhang P, Chen G, Zhou Y Front Genet. 2021; 11:599548.

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Radiation-induced alternative transcripts as detected in total and polysome-bound mRNA.

Wahba A, Ryan M, Shankavaram U, Camphausen K, Tofilon P Oncotarget. 2018; 9(1):691-705.

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References

Sandberg R, Neilson J, Sarma A, Sharp P, Burge C . Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science. 2008; 320(5883):1643-7. PMC: 2587246. DOI: 10.1126/science.1155390. View

Ingolia N, Ghaemmaghami S, Newman J, Weissman J . Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science. 2009; 324(5924):218-23. PMC: 2746483. DOI: 10.1126/science.1168978. View

Viegas M, Gehring N, Breit S, Hentze M, Kulozik A . The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway. Nucleic Acids Res. 2007; 35(13):4542-51. PMC: 1935013. DOI: 10.1093/nar/gkm461. View

Forrest A, Kawaji H, Rehli M, Baillie J, de Hoon M, Haberle V . A promoter-level mammalian expression atlas. Nature. 2014; 507(7493):462-70. PMC: 4529748. DOI: 10.1038/nature13182. View

Agarwal V, Bulun S, Leitch M, Rohrich R, Simpson E . Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab. 1996; 81(11):3843-9. DOI: 10.1210/jcem.81.11.8923826. View

Yeo J, Ng H . The transcriptional regulation of pluripotency. Cell Res. 2012; 23(1):20-32. PMC: 3541660. DOI: 10.1038/cr.2012.172. View

Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, OHanlon D, Sung H . An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell. 2011; 147(1):132-46. DOI: 10.1016/j.cell.2011.08.023. View

Guttman M, Russell P, Ingolia N, Weissman J, Lander E . Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell. 2013; 154(1):240-51. PMC: 3756563. DOI: 10.1016/j.cell.2013.06.009. View

Aubert J, Stavridis M, Tweedie S, OReilly M, Vierlinger K, Li M . Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice. Proc Natl Acad Sci U S A. 2003; 100 Suppl 1:11836-41. PMC: 304095. DOI: 10.1073/pnas.1734197100. View

10.

Hausser J, Syed A, Bilen B, Zavolan M . Analysis of CDS-located miRNA target sites suggests that they can effectively inhibit translation. Genome Res. 2013; 23(4):604-15. PMC: 3613578. DOI: 10.1101/gr.139758.112. View

11.

Ibi M, Zou P, Inoko A, Shiromizu T, Matsuyama M, Hayashi Y . Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein. J Cell Sci. 2011; 124(Pt 6):857-64. DOI: 10.1242/jcs.075705. View

12.

Au K, Sebastiano V, Afshar P, Durruthy J, Lee L, Williams B . Characterization of the human ESC transcriptome by hybrid sequencing. Proc Natl Acad Sci U S A. 2013; 110(50):E4821-30. PMC: 3864310. DOI: 10.1073/pnas.1320101110. View

13.

Mattijssen S, Welting T, Pruijn G . RNase MRP and disease. Wiley Interdiscip Rev RNA. 2011; 1(1):102-16. DOI: 10.1002/wrna.9. View

14.

Theunissen T, Jaenisch R . Molecular control of induced pluripotency. Cell Stem Cell. 2014; 14(6):720-34. PMC: 4112734. DOI: 10.1016/j.stem.2014.05.002. View

15.

Inoko A, Matsuyama M, Goto H, Ohmuro-Matsuyama Y, Hayashi Y, Enomoto M . Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells. J Cell Biol. 2012; 197(3):391-405. PMC: 3341160. DOI: 10.1083/jcb.201106101. View

16.

de Klerk E, Venema A, Anvar S, Goeman J, Hu O, Trollet C . Poly(A) binding protein nuclear 1 levels affect alternative polyadenylation. Nucleic Acids Res. 2012; 40(18):9089-101. PMC: 3467053. DOI: 10.1093/nar/gks655. View

17.

Ruiz-Orera J, Messeguer X, Subirana J, Alba M . Long non-coding RNAs as a source of new peptides. Elife. 2014; 3:e03523. PMC: 4359382. DOI: 10.7554/eLife.03523. View

18.

Licatalosi D, Darnell R . RNA processing and its regulation: global insights into biological networks. Nat Rev Genet. 2009; 11(1):75-87. PMC: 3229837. DOI: 10.1038/nrg2673. View

19.

Fabian M, Sonenberg N, Filipowicz W . Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010; 79:351-79. DOI: 10.1146/annurev-biochem-060308-103103. View

20.

Ying Q, Stavridis M, Griffiths D, Li M, Smith A . Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol. 2003; 21(2):183-6. DOI: 10.1038/nbt780. View