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  • Review Article
  • Published:

Adult-specific functions of animal microRNAs

Key Points

  • MicroRNAs (miRNAs) are actively involved in diverse aspects of adult physiology, including in stem cells, in the nervous system, cardiovascular system and during metabolism and ageing.

  • In the context of cancer development, miRNAs could serve either as tumour suppressors or as oncogenes in a tissue-dependent manner.

  • Continuous functions of miRNAs during adulthood and availability of methodologies for miRNA manipulation make miRNAs promising as therapeutic targets and agents.

  • We evaluate the strengths and weaknesses of current methods to study miRNA functions specifically in the adults.

Abstract

MicroRNAs (miRNAs) are ~22 nt RNAs that coordinate vast regulatory networks in animals and thereby influence myriad processes. This Review examines evidence that miRNAs have continuous roles in adults in ways that are separable from developmental control. Adult-specific activities for miRNAs have been described in various stem cell populations, in the context of neural function and cardiovascular biology, in metabolism and ageing, and during cancer. In addition to reviewing recent results, we also discuss methods for studying miRNA activities specifically in adults and evaluate their relative strengths and weaknesses. A fuller understanding of continuous functions of miRNAs in adults has bearing on efforts and opportunities to manipulate miRNAs for therapeutic purposes.

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Figure 1: Major strategies for analysing miRNA loss-of-function in vivo.
Figure 2: miRNA function in adult stem cell lineages.
Figure 3: Multiple functions of an individual miRNA in adult neural differentiation and function.
Figure 4: Active and continuous roles for miRNAs in cancer.

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Acknowledgements

We thank J. Mendell, A. Tarakhovsky, and A. Ventura for discussions. Work in E.C.L.'s group was supported by the Burroughs Wellcome Fund and the US National Institutes of Health and US National Institute of General Medical Sciences (R01-GM083300). The content is solely the responsibility of the authors and does not necessarily represent the official views of these agencies.

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Glossary

Argonaute

A family of effector proteins that bind small RNAs (such as microRNAs) and mediate their regulatory effect on target transcripts.

Dicer

An RNase III enzyme that processes precursor microRNA hairpins or long double-stranded RNAs (dsRNAs) into dsRNA duplexes of ~21–22 base pairs.

miRNA seed sequences

The nucleotides positioned 2–8 nt from the 5′ end of a microRNA. MicroRNAs predominantly function through base pairing between the seed region and target mRNA 3′ untranslated region.

drosha

Encodes an RNase III enzyme that cleaves primary microRNA transcripts (pri-miRNAs) into hairpin structure called precursor microRNAs, which become substrates for Dicer processing.

pasha

Encodes a double-stranded RNA-binding protein that complexes with Drosha to cleave primary microRNA transcripts into precursor microRNA hairpins. It is called DGCR8 (DiGeorge syndrome chromosomal region 8) in vertebrates.

Leptotene

The first stage of meiotic prophase. Chromosomes begin to condense.

Zygotene

The second stage of meiotic prophase. Homologous chromosome pairs are formed.

Meiotic sex chromosome inactivation

(MSCI). The transcriptional silencing of the X and Y chromosomes during the meiotic phase of spermatogenesis.

Transit-amplifying cells

A type of rapidly-dividing progenitor cell capable of dividing a finite number of times before differentiation.

Long-term potentiation

Activity-dependent, long-lasting enhancement of synaptic transmission between neurons.

Contextual fear memory

A form of fear memory established through association of aversive stimuli (for example, electric shock) with a particular neutral context.

GW182

A glycine–tryptophan repeat-containing protein that interacts with the microRNA-induced silencing complex (miRISC) to recruit proteins that mediate degradation or translational repression of target mRNAs.

Locked nucleic acid

(LNA). LNAs are a class of RNA analogues in which the 2′ oxygen and the 4′ carbon positions in the ribose ring are connected or 'locked' to create increased thermal stability relative to DNA or RNA when they are complexed with complementary DNA or RNA.

Heterochronic

Heterochronic genes determine the stage-specific temporal state of an organism during its development.

Hub cells

10–15 somatic cells residing at the apical tip of the Drosophila melanogaster testis that contact and maintain the neighbouring germline stem cells.

Oncomir addiction

Continuous dependence of tumour cells on the oncogenic microRNA (oncomir) for the maintenance of the malignant phenotype.

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Sun, K., Lai, E. Adult-specific functions of animal microRNAs. Nat Rev Genet 14, 535–548 (2013). https://doi.org/10.1038/nrg3471

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