mRNA Cap methylation in pluripotency and differentiation

Laura Grasso; Olga Suska; Lindsay Davidson; Thomas Gonatopoulos-Pournatzis; Ritchie Williamson; Lize Wasmus; Simone Wiedlich; Mark Peggie; Marios P. Stavridis; Victoria H. Cowling

doi:10.1016/j.celrep.2016.06.089

mRNA Cap methylation in pluripotency and differentiation

Laura Grasso, Olga Suska, Lindsay Davidson, Thomas Gonatopoulos-Pournatzis, Ritchie Williamson, Lize Wasmus, Simone Wiedlich, Mark Peggie, Marios P. Stavridis, Victoria H. Cowling (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

227 Downloads (Pure)

Abstract

The mRNA cap recruits factors essential for transcript processing and translation initiation. We report that regulated mRNA cap methylation is a feature of embryonic stem cell (ESC) differentiation. Expression of the mRNA cap methyltransferase activating subunit RAM is elevated in ESCs, resulting in high levels of mRNA cap methylation and expression of a cohort of pluripotency-associated genes. During neural differentiation, RAM is suppressed, resulting in repression of pluripotency-associated factors and expression of a cohort of neural-associated genes. An established requirement of differentiation is increased ERK1/2 activity, which suppresses pluripotency-associated genes. During differentiation, ERK1/2 phosphorylates RAM serine-36, targeting it for ubiquitination and proteasomal degradation, ultimately resulting in changes in gene expression associated with loss of pluripotency. Elevated RAM expression also increases the efficiency of fibroblast reprogramming. Thus, the mRNA cap emerges as a dynamic mark that instructs change in gene expression profiles during differentiation and reprogramming.

Original language	English
Pages (from-to)	1352-1365
Number of pages	14
Journal	Cell Reports
Volume	16
Issue number	5
Early online date	21 Jul 2016
DOIs	https://doi.org/10.1016/j.celrep.2016.06.089
Publication status	Published - 2 Aug 2016

Access to Document

10.1016/j.celrep.2016.06.089Licence: CC BY

Final Published Version
© 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 3.76 MBLicence: CC BY

Investigating MRNA Methyl Cap Regulation, Function and Therapeutic Potential (Senior Non-Clinical Fellowship)
Cowling, V. (Investigator)
Medical Research Council
1/01/14 → 31/12/21
Project: Research
Aref#d: 19352. The Mechanism of Myc function in cell proliferation and cancer (Career Development Fellowship)
Cowling, V. (Investigator)
3/12/07 → 2/01/14
Project: Research

Investigating the role and regulation of mRNA capping in pluripotency and differentiation
Suska, O. (Author), Cowling, V. (Supervisor), 2017
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cowling, Victoria
- Molecular Cell and Developmental Biology - Associate Staff of Biology
Person: Associate Staff

Cite this

@article{02bdaaf509484b7dacc9709596488b1d,

title = "mRNA Cap methylation in pluripotency and differentiation",

abstract = "The mRNA cap recruits factors essential for transcript processing and translation initiation. We report that regulated mRNA cap methylation is a feature of embryonic stem cell (ESC) differentiation. Expression of the mRNA cap methyltransferase activating subunit RAM is elevated in ESCs, resulting in high levels of mRNA cap methylation and expression of a cohort of pluripotency-associated genes. During neural differentiation, RAM is suppressed, resulting in repression of pluripotency-associated factors and expression of a cohort of neural-associated genes. An established requirement of differentiation is increased ERK1/2 activity, which suppresses pluripotency-associated genes. During differentiation, ERK1/2 phosphorylates RAM serine-36, targeting it for ubiquitination and proteasomal degradation, ultimately resulting in changes in gene expression associated with loss of pluripotency. Elevated RAM expression also increases the efficiency of fibroblast reprogramming. Thus, the mRNA cap emerges as a dynamic mark that instructs change in gene expression profiles during differentiation and reprogramming.",

author = "Laura Grasso and Olga Suska and Lindsay Davidson and Thomas Gonatopoulos-Pournatzis and Ritchie Williamson and Lize Wasmus and Simone Wiedlich and Mark Peggie and Stavridis, {Marios P.} and Cowling, {Victoria H.}",

note = "We thank the Findlay, M.P.S., and V.H.C. lab members. Research was funded by an MRC Senior Fellowship (MR/K024213/1 to V.H.C.), a Lister Institute Prize Fellowship (to V.H.C.), Wellcome Trust PhD studentships (097462/Z/11/Z to L.G. and O.S.), and the University of Dundee Human Pluripotent Stem Cell Facility. Research was supported by Wellcome Institutional Support Fund 097818/Z/11/B, GRE Centre Award 097945/Z/11/Z, and the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KGaA, Janssen Pharmaceutica, and Pfizer).",

year = "2016",

month = aug,

day = "2",

doi = "10.1016/j.celrep.2016.06.089",

language = "English",

volume = "16",

pages = "1352--1365",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - mRNA Cap methylation in pluripotency and differentiation

AU - Grasso, Laura

AU - Suska, Olga

AU - Davidson, Lindsay

AU - Gonatopoulos-Pournatzis, Thomas

AU - Williamson, Ritchie

AU - Wasmus, Lize

AU - Wiedlich, Simone

AU - Peggie, Mark

AU - Stavridis, Marios P.

AU - Cowling, Victoria H.

N1 - We thank the Findlay, M.P.S., and V.H.C. lab members. Research was funded by an MRC Senior Fellowship (MR/K024213/1 to V.H.C.), a Lister Institute Prize Fellowship (to V.H.C.), Wellcome Trust PhD studentships (097462/Z/11/Z to L.G. and O.S.), and the University of Dundee Human Pluripotent Stem Cell Facility. Research was supported by Wellcome Institutional Support Fund 097818/Z/11/B, GRE Centre Award 097945/Z/11/Z, and the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KGaA, Janssen Pharmaceutica, and Pfizer).

PY - 2016/8/2

Y1 - 2016/8/2

N2 - The mRNA cap recruits factors essential for transcript processing and translation initiation. We report that regulated mRNA cap methylation is a feature of embryonic stem cell (ESC) differentiation. Expression of the mRNA cap methyltransferase activating subunit RAM is elevated in ESCs, resulting in high levels of mRNA cap methylation and expression of a cohort of pluripotency-associated genes. During neural differentiation, RAM is suppressed, resulting in repression of pluripotency-associated factors and expression of a cohort of neural-associated genes. An established requirement of differentiation is increased ERK1/2 activity, which suppresses pluripotency-associated genes. During differentiation, ERK1/2 phosphorylates RAM serine-36, targeting it for ubiquitination and proteasomal degradation, ultimately resulting in changes in gene expression associated with loss of pluripotency. Elevated RAM expression also increases the efficiency of fibroblast reprogramming. Thus, the mRNA cap emerges as a dynamic mark that instructs change in gene expression profiles during differentiation and reprogramming.

AB - The mRNA cap recruits factors essential for transcript processing and translation initiation. We report that regulated mRNA cap methylation is a feature of embryonic stem cell (ESC) differentiation. Expression of the mRNA cap methyltransferase activating subunit RAM is elevated in ESCs, resulting in high levels of mRNA cap methylation and expression of a cohort of pluripotency-associated genes. During neural differentiation, RAM is suppressed, resulting in repression of pluripotency-associated factors and expression of a cohort of neural-associated genes. An established requirement of differentiation is increased ERK1/2 activity, which suppresses pluripotency-associated genes. During differentiation, ERK1/2 phosphorylates RAM serine-36, targeting it for ubiquitination and proteasomal degradation, ultimately resulting in changes in gene expression associated with loss of pluripotency. Elevated RAM expression also increases the efficiency of fibroblast reprogramming. Thus, the mRNA cap emerges as a dynamic mark that instructs change in gene expression profiles during differentiation and reprogramming.

U2 - 10.1016/j.celrep.2016.06.089

DO - 10.1016/j.celrep.2016.06.089

M3 - Article

C2 - 27452456

SN - 2211-1247

VL - 16

SP - 1352

EP - 1365

JO - Cell Reports

JF - Cell Reports

IS - 5

ER -

mRNA Cap methylation in pluripotency and differentiation

Abstract

Access to Document

Fingerprint

Projects

Investigating MRNA Methyl Cap Regulation, Function and Therapeutic Potential (Senior Non-Clinical Fellowship)

Aref#d: 19352. The Mechanism of Myc function in cell proliferation and cancer (Career Development Fellowship)

Student theses

Investigating the role and regulation of mRNA capping in pluripotency and differentiation

Profiles

Cowling, Victoria

Cite this