Cited by 1,384MicroRNA in disease regulationRNA and protein synthesis mechanismsPI3K/AKT/mTOR signaling in cancer

MicroRNA-10a binds the 5’UTR of ribosomal protein mRNAs and enhances their translation

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Ørom, Ulf Andersson, Nielsen, Finn Cilius, Lund, Anders H.·2008·Molecular Cell

Abstract

MicroRNAs (miRNAs) are small RNAs that function as posttranscriptional regulators of gene expression. miRNAs affect a variety of signaling pathways, and impaired miRNA regulation may contribute to the development of cancer and other diseases. Here we show that miRNA miR-10a interacts with the 5' untranslated region of mRNAs encoding ribosomal proteins to enhance their translation. miR-10a alleviates translational repression of the ribosomal protein mRNAs during amino acid starvation and is required for their translational induction following anisomycin treatment or overexpression of RAS. We show that miR-10a binds immediately downstream of the regulatory 5'TOP motif and that the 5'TOP regulatory complex and miR-10a are functionally interconnected. The results show that miR-10a may positively control global protein synthesis via the stimulation of ribosomal protein mRNA translation and ribosome biogenesis and hereby affect the ability of cells to undergo transformation.

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Crossref · 10.1016/j.molcel.2008.05.001

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  • RBPs can compete for binding to microRNA, thereby having either synergistic or opposing effects on RNA stability.

    “In addition, RBPs can compete for binding to microRNA, thereby having either synergistic or opposing effects on RNA stability [38,39,40].”

    From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [38]

    The Discussion (page not available) speculates that miR-10a competes with an unidentified negative regulator near the 5′TOP motif, which gives limited support for competition involving a microRNA. It does not identify that regulator as an RBP or report synergistic or opposing effects on RNA stability. The Results instead say RP mRNA levels were unaffected and describe predominantly translational regulation. (LLM, conf=0.84)

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Research works printed but not linked: 2

  1. [1]1. Averous, J. ∙ Proud, C.G. When translation meets transformation: the mTOR story Oncogene. 2006; 25:6423-6435 Crossref Scopus (173) PubMed Google Scholar
  2. [2]2. Bassoe, C.F. ∙ Bruserud, O. ∙ Pryme, I.F. ... Ribosomal proteins sustain morphology, function and phenotype in acute myeloid leukemia blasts Leuk. Res. 1998; 22:329-339

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Authors
Ørom, U. A., Nielsen, F. C., & Lund, A. H.
Affiliations
University of Copenhagen (DK)
Corresponding author
Lund, Anders H.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2008-05
Volume
30
Issue
4
Pages
460-471
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2046314136
Cited by
1,384
References
5
Citations by year
2026: 19 · 2025: 48 · 2024: 49 · 2023: 60 · 2022: 71 · 2021: 83 · 2020: 51 · 2019: 65 · 2018: 62 · 2017: 89 · 2016: 86 · 2015: 83 · 2014: 126 · 2013: 104 · 2012: 124
FWCI
27.97
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
Funders
Lundbeckfonden (R31-2007-1447)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
miR-10a, microRNA, ribosomal protein mRNAs, 5' untranslated region, translational regulation, protein synthesis inhibition, amino acid starvation, Ras signaling, anisomycin, ribosome biogenesis, post-transcriptional regulation, cell transformation
MeSH terms
Amino Acids, Animals, Base Sequence, Binding Sites, Cell Transformation, Neoplastic, HeLa Cells, Humans, Membrane Glycoproteins, Molecular Sequence Data, Receptors, Immunologic, Ribosomal Proteins, Protein Biosynthesis, 5' Untranslated Regions, NIH 3T3 Cells, Mice, Rats

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