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Mammalian microRNAs predominantly act to decrease target mRNA levels

Author

Listed:
  • Huili Guo

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Nicholas T. Ingolia

    (University of California
    California Institute for Quantitative Biosciences)

  • Jonathan S. Weissman

    (University of California
    California Institute for Quantitative Biosciences)

  • David P. Bartel

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

Abstract

MicroRNAs (miRNAs) are endogenous ∼22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.

Suggested Citation

  • Huili Guo & Nicholas T. Ingolia & Jonathan S. Weissman & David P. Bartel, 2010. "Mammalian microRNAs predominantly act to decrease target mRNA levels," Nature, Nature, vol. 466(7308), pages 835-840, August.
    • Handle: RePEc:nat:nature:v:466:y:2010:i:7308:d:10.1038_nature09267
    DOI: 10.1038/nature09267
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    1. Yasemin Oztemur & Tufan Bekmez & Alp Aydos & Isik G Yulug & Betul Bozkurt & Bala Gur Dedeoglu, 2015. "A Ranking-Based Meta-Analysis Reveals Let-7 Family as a Meta-Signature for Grade Classification in Breast Cancer," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-16, May.
    2. Urmo Võsa & Tõnu Esko & Silva Kasela & Tarmo Annilo, 2015. "Altered Gene Expression Associated with microRNA Binding Site Polymorphisms," PLOS ONE, Public Library of Science, vol. 10(10), pages 1-24, October.
    3. Mary P. LaPierre & Katherine Lawler & Svenja Godbersen & I. Sadaf Farooqi & Markus Stoffel, 2022. "MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Evelyn Zacharewicz & Paul Della Gatta & John Reynolds & Andrew Garnham & Tamsyn Crowley & Aaron P Russell & Séverine Lamon, 2014. "Identification of MicroRNAs Linked to Regulators of Muscle Protein Synthesis and Regeneration in Young and Old Skeletal Muscle," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-25, December.
    5. Laura Ann Jacobs & Findlay Bewicke-Copley & Mark Graham Poolman & Ryan Charles Pink & Laura Ann Mulcahy & Isabel Baker & Ellie-May Beaman & Travis Brooks & Daniel Paul Caley & William Cowling & James , 2013. "Meta-Analysis Using a Novel Database, miRStress, Reveals miRNAs That Are Frequently Associated with the Radiation and Hypoxia Stress-Responses," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-1, November.
    6. Joel W Graff & Linda S Powers & Anne M Dickson & Jongkwang Kim & Anna C Reisetter & Ihab H Hassan & Karol Kremens & Thomas J Gross & Mary E Wilson & Martha M Monick, 2012. "Cigarette Smoking Decreases Global MicroRNA Expression in Human Alveolar Macrophages," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-13, August.
    7. Chen-Ching Lin & Ramkrishna Mitra & Zhongming Zhao, 2014. "A Tri-Component Conservation Strategy Reveals Highly Confident MicroRNA-mRNA Interactions and Evolution of MicroRNA Regulatory Networks," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-8, July.
    8. Shuangmei Tian & Ziyu Zhao & Beibei Ren & Degeng Wang, 2024. "Non-Linear Relationship between MiRNA Regulatory Activity and Binding Site Counts on Target mRNAs," Data, MDPI, vol. 9(10), pages 1-13, September.
    9. Ray M Marín & Jiří Vaníček, 2012. "Optimal Use of Conservation and Accessibility Filters in MicroRNA Target Prediction," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-11, February.
    10. Youjia Hua & Shiwei Duan & Andrea E Murmann & Niels Larsen & Jørgen Kjems & Anders H Lund & Marcus E Peter, 2011. "miRConnect: Identifying Effector Genes of miRNAs and miRNA Families in Cancer Cells," PLOS ONE, Public Library of Science, vol. 6(10), pages 1-16, October.
    11. Charlotte A. Cialek & Gabriel Galindo & Tatsuya Morisaki & Ning Zhao & Taiowa A. Montgomery & Timothy J. Stasevich, 2022. "Imaging translational control by Argonaute with single-molecule resolution in live cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Agnieszka Boroń & Małgorzata Śmiarowska & Anna Grzywacz & Krzysztof Chmielowiec & Jolanta Chmielowiec & Jolanta Masiak & Tomasz Pawłowski & Dariusz Larysz & Andrzej Ciechanowicz, 2022. "Association of Polymorphism within the Putative miRNA Target Site in the 3′UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder," IJERPH, MDPI, vol. 19(16), pages 1-21, August.
    13. Catherine Mooney & Rana Raoof & Hany El-Naggar & Amaya Sanz-Rodriguez & Eva M Jimenez-Mateos & David C Henshall, 2015. "High Throughput qPCR Expression Profiling of Circulating MicroRNAs Reveals Minimal Sex- and Sample Timing-Related Variation in Plasma of Healthy Volunteers," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-20, December.

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