Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells
Open accessPublished version of a preprint
Abstract
Translation and mRNA degradation are intimately connected, yet the mechanisms that link them are not fully understood. Here, we studied these mechanisms in embryonic stem cells (ESCs). Transcripts showed a wide range of stabilities, which correlated with their relative translation levels and that did not change during early ESC differentiation. The protein DHH1 links translation to mRNA stability in yeast; however, loss of the mammalian homolog, DDX6, in ESCs did not disrupt the correlation across transcripts. Instead, the loss of DDX6 led to upregulated translation of microRNA targets, without concurrent changes in mRNA stability. The Ddx6 knockout cells were phenotypically and molecularly similar to cells lacking all microRNAs (Dgcr8 knockout ESCs). These data show that the loss of DDX6 can separate the two canonical functions of microRNAs: translational repression and transcript destabilization. Furthermore, these data uncover a central role for translational repression independent of transcript destabilization in defining the downstream consequences of microRNA loss.
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References 81 · Cited by 69
- Authors
- Freimer, J. W., Hu, T., & Blelloch, R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Blelloch, Robert
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-07-25
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6086665
- OpenAlex
- W2799325067
- Cited by
- 69
- References
- 81
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 4 · 2023: 3 · 2022: 14 · 2021: 5 · 2020: 17 · 2019: 14
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute of General Medical Sciences (GM101180, GM122439)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- microRNA, protein synthesis inhibition, mRNA degradation, embryonic stem cells, DDX6, Dhh1, mRNA stability, DGCR8, microRNA loss, stem cell differentiation
- MeSH terms
- Animals, Cell Differentiation, Humans, Peptide Chain Termination, Translational, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Protein Biosynthesis, RNA-Binding Proteins, RNA Stability, Saccharomyces cerevisiae Proteins, MicroRNAs, Mice, DEAD-box RNA Helicases, Embryonic Stem Cells, Gene Knockout Techniques
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