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RARs and MicroRNAs

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The Biochemistry of Retinoic Acid Receptors I: Structure, Activation, and Function at the Molecular Level

Part of the book series: Subcellular Biochemistry ((SCBI,volume 70))

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs acting as endogenous regulators of gene expression. Their discovery is one of the major recent breakthroughs in molecular biology. miRNAs establish a multiplicity of relationships with target mRNAs and exert pleiotropic biological effects in many cell physiological pathways during development and adult life. The dynamic nature of gene expression regulation by Retinoic Acid (RA) is consistent with an extensive functional interplay with miRNA activities. In fact, RA regulates the expression of many different miRNAs, thus suggesting a relevant function of miRNAs in RA-controlled gene expression programmes. miRNAs have been extensively studied as targets and mediators of the biological activity of RA during embryonic development as well as in normal and neoplastic cells. However, relatively few studies have experimentally explored the direct contribution of miRNA function to the RA signalling pathway. Here, we provide an overview of the mechanistic aspects that allow miRNA biogenesis, functional activation and regulation, focusing on recent evidence that highlights a functional interplay between miRNAs and RA-regulated molecular networks. We report examples of tissue-specific roles of miRNAs modulated by RA in stem cell pluripotency maintenance and regeneration, embryonic development, hematopoietic and neural differentiation, and other biological model systems, underlining their role in disease pathogenesis. We also address novel areas of research linking the RA signalling pathway to the nuclear activity of miRNAs.

It is now clear an extensive miRNA world was flying almost unseen by our genetic radar. As much as geneticists like to think that nothing can escape genetic analysis, the miRNA genes are so small that they almost escaped our notice [124].

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Abbreviations

Ago:

Argonaute

ALDH1A2:

Aldehyde dehydrogenase-1a2

AML:

Acute myeloid leukemia

APL:

Acute promyelocytic leukemia

C/EBPα:

CCAAT/enhancer-binding protein-alpha

ceRNAs:

Competing endogenous RNAs

DGCR8:

DiGeorge syndrome critical region gene 8

ESC:

Embryonic stem cells

HDAC:

Histone deacetylase

Hox:

Homeobox

HPCs:

Hematopoietic progenitor cells

HSC:

Hematopoietic stem cells

lncRNA:

Long non-coding RNA

miRNAs:

MicroRNAs

NFI-A:

Nuclear factor I-A

PACT:

Protein kinase R (PKR) activator

P-bodies:

Processing bodies

PcG:

Polycomb group proteins

Pitx3:

Paired-like homeodomain transcription factor 3

pre-miRNA:

MicroRNA precursor

pri-miRNA:

Primary microRNA

PTB:

Polypyrimidine tract binding protein

RA:

Retinoic Acid

RALDH2:

Retinaldehyde dehydrogenase 2

RAR:

Retinoic acid receptor

RISC:

RNA-induced silencing complex

RNA polymerase II:

RNA polII

RXR:

Retinoid X receptor

TF:

Transcription factor

TRBP:

Trans-activation response (TAR) RNA-binding protein

UTR:

Untranslated region

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Authors and Affiliations

  1. Department of Medical-Surgical Sciences and Biotechnologies, University “La Sapienza”, Rome, Italy

    Clara Nervi

  2. Department of Clinical and Experimental Medicine, General Pathology, University of Perugia, Perugia, Italy

    Francesco Grignani

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  1. Department of Biological Sciences, Tennessee State University, Nashville, Tennessee, USA

    Mary Ann Asson-Batres

  2. IGBMC, Illkirch Cedex, France

    Cécile Rochette-Egly

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Nervi, C., Grignani, F. (2014). RARs and MicroRNAs. In: Asson-Batres, M., Rochette-Egly, C. (eds) The Biochemistry of Retinoic Acid Receptors I: Structure, Activation, and Function at the Molecular Level. Subcellular Biochemistry, vol 70. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9050-5_8

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