Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Jan 30:5:8.
doi: 10.3389/fgene.2014.00008. eCollection 2014.

Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation

Reena V Kartha  1 , Subbaya Subramanian  2
Affiliations
Review

Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation

Reena V Kartha et al. Front Genet. .

Abstract

The discovery of microRNAs (miRNAs) has led to a paradigm shift in our basic understanding of gene regulation. Competing endogenous RNAs (ceRNAs) are the recent entrants adding to the complexities of miRNA mediated gene regulation. ceRNAs are RNAs that share miRNA recognition elements (MREs) thereby regulating each other. It is apparent that miRNAs act as rheostats that fine-tune gene expression and maintain the functional balance of various gene networks. Thus MREs in coding and non-coding transcripts have evolved to become the crosstalk hubs of gene interactions, affecting the expression levels and activities of different ceRNAs. Decoding the crosstalk between MREs mediated by ceRNAs is critical to delineate the intricacies in gene regulation, and we have just begun to unravel this complexity.

Keywords: MREs; RNA-RNA crosstalk; competing endogenous RNAs; miRNAs ceRNAs; microRNAs; sponge effect.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representation of ceRNAs mediated gene regulation. The regulation of miRNAs and mRNAs are mutual; as a consequence, levels of mRNA(s) containing relevant MREs could affect the levels and activity of another mRNA. The cross talk between mRNAs mediated by the MREs depends on the number and frequency of specific type of MREs. This cross talk is significantly influenced by the number and frequency of relevant MREs in the transcriptome of a given cell. The ceRNA-miRNA-mRNA cross talk maintains the overall activity and functional balance of gene networks in a cell. The ceRNA mediated regulation of mRNA-Y is illustrated here. mRNA-Y is a functional target of miR-B. However, the expression levels of mRNA-X that contains MREs for miRNA-B can act like a sponge to sequester the effect of miR-B on mRNA-Y (indicated with bold red line). Hence a decrease in expression levels of mRNA-X can also decrease the levels of mRNA-Y.
Figure 2
Figure 2
cis and trans regulation of mRNA. The MREs in the 3′UTR of mRNA can act as cis regulatory elements affecting its own stability and levels via miRNAs. On the other hand, MREs in the mRNAs functioning as ceRNAs can regulate the levels and activity of another mRNA by trans regulation.
Figure 3
Figure 3
Interactions between different types of ceRNAs, miRNA, and mRNA. Coding RNAs and non-coding RNAs including pseudogenes, lncRNAs, and circular RNAs can function as ceRNAs.
See this image and copyright information in PMC

References

    1. Ala U., Karreth F. A., Bosia C., Pagnani A., Taulli R., Leopold V., et al. (2013). Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments. Proc. Natl. Acad. Sci. U.S.A. 110, 7154–7159 10.1073/pnas.1222509110 - DOI - PMC - PubMed
    1. Alimonti A., Carracedo A., Clohessy J. G., Trotman L. C., Nardella C., Egia A., et al. (2010). Subtle variations in Pten dose determine cancer susceptibility. Nat. Genet. 42, 454–458 10.1038/ng.556 - DOI - PMC - PubMed
    1. Arroyo J. D., Chevillet J. R., Kroh E. M., Ruf I. K., Pritchard C. C., Gibson D. F., et al. (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. U.S.A. 108, 5003–5008 10.1073/pnas.1019055108 - DOI - PMC - PubMed
    1. Arvey A., Larsson E., Sander C., Leslie C. S., Marks D. S. (2010). Target mRNA abundance dilutes microRNA and siRNA activity. Mol. Syst. Biol. 6, 363 10.1038/msb.2010.24 - DOI - PMC - PubMed
    1. Aung K., Lin S. I., Wu C. C., Huang Y. T., Su C. L., Chiou T. J. (2006). pho2, a phosphate overaccumulator, is caused by a nonsense mutation in a microRNA399 target gene. Plant Physiol. 141, 1000–1011 10.1104/pp.106.078063 - DOI - PMC - PubMed

LinkOut - more resources