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Updated: Jun 19, 2025
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Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts
Published on: January 2, 2018
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Poised PABP-RNA hubs implement signal-dependent mRNA decay in development
Miha Modic1,2,3, Klara Kuret4,5,6, Sebastian Steinhauser4
1The Francis Crick Institute, London, UK. miha.modic@kcl.ac.uk.
Nature Structural & Molecular Biology
|July 25, 2024
Summary
Extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase kinase (MEK) signaling rapidly degrade naive pluripotency mRNAs. This process, regulated by LIN28A and poly(A)-binding protein (PABP), enables developmental progression.
Area of Science:
- Molecular Biology
- Developmental Biology
- Gene Regulation
Background:
- Cell fate transitions are driven by signaling pathways altering gene expression.
- Mechanisms for rapid and selective transcriptome rewiring in response to signaling remain unclear.
Purpose of the Study:
- To elucidate the mechanisms of extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase kinase (MEK)-induced decay of naive pluripotency mRNAs.
- To identify sequence determinants and trans-acting regulators involved in this decay process.
Main Methods:
- Deep learning analysis to identify sequence determinants and trans-acting regulators.
- Investigated the role of LIN28A phosphorylation and its interaction with poly(A)-binding protein (PABP).
Main Results:
- ERK-MEK signaling phosphorylates LIN28A, promoting its interaction with PABP at the 3' untranslated regions (3'UTRs) of naive pluripotency mRNAs.
- AUU motifs in 3'UTRs facilitate LIN28A-PABP convergence, enhancing PABP binding and promoting mRNA decay.
- This rapid decay enables the transition from naive to primed pluripotency.
Conclusions:
- Signal-induced convergence of LIN28A and PABP-RNA hubs drives selective decay of naive mRNAs.
- This mechanism facilitates rapid transcriptome remodeling essential for developmental progression, such as embryo implantation.
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