Nuclear Retention of mRNA in Mammalian Tissues
Open accessAbstract
mRNA is thought to predominantly reside in the cytoplasm, where it is translated and eventually degraded. Although nuclear retention of mRNA has a regulatory potential, it is considered extremely rare in mammals. Here, to explore the extent of mRNA retention in metabolic tissues, we combine deep sequencing of nuclear and cytoplasmic RNA fractions with single-molecule transcript imaging in mouse beta cells, liver, and gut. We identify a wide range of protein-coding genes for which the levels of spliced polyadenylated mRNA are higher in the nucleus than in the cytoplasm. These include genes such as the transcription factor ChREBP, Nlrp6, Glucokinase, and Glucagon receptor. We demonstrate that nuclear retention of mRNA can efficiently buffer cytoplasmic transcript levels from noise that emanates from transcriptional bursts. Our study challenges the view that transcripts predominantly reside in the cytoplasm and reveals a role of the nucleus in dampening gene expression noise.
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Cytoplasmic RNA is enriched among genes more abundant in cells.
“cytoplasmic RNA (defined by Bahar Halpern et al., 2015) was clearly enriched among genes found to be more abundant in cells (NES = −2.03, padj = 3.6e-05)”
From Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans (2020) · cites this paper as Bahar Halpern et al., 2015
Recent progress in epigenome analysis has included assays for single-cell ChIP-seq (Drop-ChIP), single-cell ATAC-seq, single-cell Hi-C, and single-cell DNA methylation.
“Although most high-throughput single-cell profiling studies to date have focused on RNA and protein, recent progress in epigenome analysis185 has included assays for single-cell ChIP-seq (Drop-ChIP26), single-cell ATAC-seq27,28, single-cell Hi-C29 (a genome-wide derivative of the chromosome conformation capture (3C) technique), and single-cell DNA methylation22–25.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [185]
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- Authors
- Bahar Halpern, K., Caspi, I., Lemze, D., Levy, M., Landen, S., Elinav, E., Ulitsky, I., & Itzkovitz, S.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Itzkovitz, Shalev
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 13
- Issue
- 12
- Pages
- 2653-2662
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4700052
- OpenAlex
- W2201924392
- Cited by
- 258
- References
- 46
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 21 · 2023: 17 · 2022: 32 · 2021: 29 · 2020: 20 · 2019: 35 · 2018: 27 · 2017: 27 · 2016: 18 · 2015: 2
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- stochastic gene expression, transcriptional bursts, polyadenylated mRNA, ChREBP, NLRP6, glucokinase, glucagon receptor, pancreatic beta cells, liver, intestine
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Liver, Male, Mice, Inbred C57BL, Nuclear Proteins, Receptors, Cell Surface, RNA, Messenger, Transcription Factors, Insulin-Secreting Cells, Mice, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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