Epiblast morphogenesis is controlled by selective mRNA decay triggered by LIN28A relocation Article Swipe
Miha Modic
,
Igor Ruiz de los Mozos
,
Sebastian Steinhauser
,
Emiel van Genderen
,
Silvia Schirge
,
Valter Bergant
,
Joël Ryan
,
Christopher B. Mulholland
,
Rupert Faraway
,
Flora Lee
,
Tajda Klobučar
,
Juliane Merl‐Pham
,
Stephanie M Hauck
,
Micha Drukker
,
Sebastian Bultmann
,
Heinrich Leonhardt
,
Heiko Lickert
,
Nicholas M. Luscombe
,
Derk ten Berge
,
Jernej Ule
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.15.433780
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.15.433780
The embryonic progression from naïve to primed pluripotency is accompanied by the rapid decay of pluripotency-associated mRNAs and a concomitant radical morphogenetic sequence of epiblast polarization, rosette formation and lumenogenesis. The mechanisms triggering and linking these events remain poorly understood. Guided by machine learning and metabolic RNA sequencing, we identified RNA binding proteins (RBPs), especially LIN28A, as primary mRNA decay factors. Using mRNA-RBP interactome capture, we revealed a dramatic increase in LIN28A mRNA binding during the naïve-rosette-primed pluripotency transition, driven by its nucleolar-to-cytoplasmic translocation. Cytoplasmic LIN28A binds to 3’UTRs of pluripotency-associated mRNAs to directly stimulate their decay and drive lumenogenesis. Accordingly, forced nuclear retention of LIN28A impeded lumenogenesis, impaired gastrulation, and caused an unforeseen embryonic multiplication. Selective mRNA decay, driven by nucleo-cytoplasmic RBP translocation, therefore acts as an intrinsic mechanism linking cell identity switches to the control of embryonic growth and morphogenesis.
Related Topics
Concepts
Epiblast
Cell biology
Gastrulation
RNA-binding protein
Embryonic stem cell
Biology
Messenger RNA
Cytoplasm
Homeobox protein NANOG
Chemistry
Embryo
Embryogenesis
Genetics
Gene
Induced pluripotent stem cell
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.03.15.433780
- https://www.biorxiv.org/content/biorxiv/early/2021/03/16/2021.03.15.433780.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 50
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3136303053
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3136303053Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2021.03.15.433780Digital Object Identifier
- Title
-
Epiblast morphogenesis is controlled by selective mRNA decay triggered by LIN28A relocationWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
-
2021-03-16Full publication date if available
- Authors
-
Miha Modic, Igor Ruiz de los Mozos, Sebastian Steinhauser, Emiel van Genderen, Silvia Schirge, Valter Bergant, Joël Ryan, Christopher B. Mulholland, Rupert Faraway, Flora Lee, Tajda Klobučar, Juliane Merl‐Pham, Stephanie M Hauck, Micha Drukker, Sebastian Bultmann, Heinrich Leonhardt, Heiko Lickert, Nicholas M. Luscombe, Derk ten Berge, Jernej UleList of authors in order
- Landing page
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https://doi.org/10.1101/2021.03.15.433780Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/03/16/2021.03.15.433780.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2021/03/16/2021.03.15.433780.full.pdfDirect OA link when available
- Concepts
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Epiblast, Cell biology, Gastrulation, RNA-binding protein, Embryonic stem cell, Biology, Messenger RNA, Cytoplasm, Homeobox protein NANOG, Chemistry, Embryo, Embryogenesis, Genetics, Gene, Induced pluripotent stem cellTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2023: 1Per-year citation counts (last 5 years)
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50Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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