Long non-coding RNAs as regulators of the endocrine system

Abstract

Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

Figure 1

Categories of long non-coding RNAs classified on the basis of their genomic region.

Figure 2

Mechanisms of lncRNA action. Most lncRNAs are nuclear and their most common mechanism of action is via recruitment of chromatin modifiers to DNA. These chromatin modifiers can be repressive (such as the PRC1/2 or the LSD1–CoREST complexes), activating (such as transcriptional mediators or the WDR5–MLL complex) or other modifiers such as hnRNPs as nuclear organization factors. Some lncRNAs bind to specific proteins and act as scaffolds within ribonucleoprotein complexes. In the cytosol, circular or linear lncRNAs can act at the post-transcriptional level as sponges for miRNAs, therefore inhibiting the actions of miRNAs on mRNAs. A few examples of lncRNAs that affect the half-life of mRNAs by either destabilizing or stabilizing a specific subset of mRNAs have been described. Abbreviations: hnRNP, heterogeneous ribonucleoprotein; lncRNA, long non-coding RNA; miRNA, microRNA; PRC, polycomb repressor complex.

Figure 3

Endocrine organs and lncRNAs. lncRNAs known to be involved in the development, physiology and/or disease of each endocrine organ are indicated in the image. lncRNAs highlighted in bold grey are involved in cancer.