miRNA: An Ancient, Small and Important Gene Regulatory Element

On formation and function of miRNAs.  Used as described by license for Wikimedia Commons.

On formation and function of miRNAs. Used under license for Wikimedia Commons.

MicroRNA (miRNA) is a group of small (approximately 18–24 nucleotide) single-stranded, non-coding RNAs that function in negative regulation of gene expression.

Lest that non-coding part make miRNA sound inconsequential, read on. While discovery of miRNA is relatively recent, miRNA is some ancient and seriously important gene regulatory material.

Identification of miRNA was published in late 1993 by Lee, Feinbaum and Ambros regarding their work with the worm, C. elegans.

miRNA has been studied in plants, mammals and even viruses, where miRNA functions to repress mRNA expression through base-pairing to complementary sequences in mRNA. This binding can silence the mRNA by several mechanisms, including cleavage of the mRNA, shortening of the poly(A) tail and interference with translation efficiency.

miRNA is well-conserved in plants and animals and thought to be both essential and an ancient part of gene regulation.

In plants, miRNA functions by inducing cleavage of mRNA. In animals, miRNA is able to bind to targets using as little as 6–8 nucleotides, called the ‘seed region’, near the 5′ end of the miRNA. This small binding region does not induce cleavage, but can be part of multiple miRNA bindings. In animals, an individual miRNA can have multiple mRNA targets, and a particular mRNA can be regulated by multiple miRNAs.

miRNA-binding sites are usually located in the 3′ untranslated region of target mRNAs.

miRNA regulation is a key component in a wide range of biological processes such as stem cell maintenance, developmental and metabolic processes, host–virus interactions, apoptosis and proliferation of cardiac and skeletal muscle (Xu, C. et al.).

Considering that miRNA is involved in stem cell biology, as well as developmental and metabolic processes, we are not surprised that a number of human diseases including cancer are associated with changes in the copy number or expression of miRNA as well as mutations in miRNA or its target mRNAs.

To gauge what is on-going in research involving miRNA, here are a few abstracts from an upcoming conference, in which miRNA is discussed in relation to disease and as biomarkers of disease:

  1. Evidence that circulating microRNAs are biomarkers for risk of type 2 diabetes.
  2. Studies have shown that specific exosomic miRNAs released by cancer cells can bind to receptors in surrounding cells and affect the biology of the tumor microenvironment.
  3. A number of miRNAs have been shown to be downregulated in several kinds of cancer including ovarian, breast, lung, colon and glioma; and that levels of miRNA suppression are associated with cancer development and drug resistance, and are involved in regulating tumor growth and angiogenesis.

An excellent recent review article on miRNA biogenesis can be found in Nature Reviews Molecular Cell Biology (2014) (doi:10.1038/nrm3838).

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Kari Kenefick

Kari has been a science writer/editor for Promega since 1996. Prior to that she enjoyed working in veterinary microbiology/immunology, and has an M.S. in Bacteriology, U of WI-Madison. Favorite topics include infectious disease, inflammation, aging, exercise, nutrition and personality traits. When not writing, she enjoys training her dogs in agility and obedience. About the practice of writing, as we say for cell-based assays, "add-mix-measure".

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