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Review
. 2016 Jul;73(13):2491-509.
doi: 10.1007/s00018-016-2174-5. Epub 2016 Mar 23.

Mechanisms of long noncoding RNA function in development and disease

Sandra U Schmitz  1 , Phillip Grote  2 , Bernhard G Herrmann  3   4
Affiliations
Review

Mechanisms of long noncoding RNA function in development and disease

Sandra U Schmitz et al. Cell Mol Life Sci. 2016 Jul.

Abstract

Since decades it has been known that non-protein-coding RNAs have important cellular functions. Deep sequencing recently facilitated the discovery of thousands of novel transcripts, now classified as long noncoding RNAs (lncRNAs), in many vertebrate and invertebrate species. LncRNAs are involved in a wide range of cellular mechanisms, from almost all aspects of gene expression to protein translation and stability. Recent findings implicate lncRNAs as key players of cellular differentiation, cell lineage choice, organogenesis and tissue homeostasis. Moreover, lncRNAs are involved in pathological conditions such as cancer and cardiovascular disease, and therefore provide novel biomarkers and pharmaceutical targets. Here we discuss examples illustrating the versatility of lncRNAs in gene control, development and differentiation, as well as in human disease.

Keywords: Cancer; Cardiovascular disease; Chromatin; Differentiation; Epigenetics; Gene regulation; Genome organization; LncRNA.

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Figures

Fig. 1
Fig. 1
Classification of lncRNAs according to their position relative to neighboring gene(s). a Divergently transcribed lncRNA originating from the same promoter region as the adjacent (usually protein coding) gene, but from the opposite strand; b convergently transcribed genes encoded on opposite strands and facing each other; c intergenic (or intervening) lncRNA (or lincRNA) located distant from other genes (usually >10 kb); d examples for various cases of lncRNAs overlapping with other genes on the same or the opposite strand; e enhancer RNAs expressed as uni- or bidirectional transcripts; f LncRNA transcribed from an intron of another gene; g lncRNA hosting a miRNA. Noncoding genes are shown in green, protein-coding genes in orange
Fig. 2
Fig. 2
Schematic representation of cellular mechanisms involving lncRNAs. a LncRNA transcripts evicting proteins from chromatin; here, pancRNAs prevent DNMT from methylating DNA in their promoter region, thereby ensuring mRNA transcription. b LncRNAs recruiting the Mediator complex to an enhancer region, stabilizing loop formation and transcription of the associated gene. c LncRNAs transcribed from an enhancer region interfering with enhancer-promoter contact, thereby inhibiting transcription of the protein-coding gene. d LncRNA recruiting proteins, such as chromatin-modifying complexes to specific target sites in the genome, e.g. via DNA-RNA triplex formation. e LncRNA acting as scaffold linking different proteins required for concerted action. f LncRNA binding and sequestering proteins to prevent or attenuate their action, e.g. binding to mRNAs (left); circRNA sequestering miRNAs to prevent their binding to mRNAs (right). g Example of a lncRNA changing the splicing pattern by binding to a primary RNA transcript. h LncRNA stabilizing a mRNA by recruiting proteins such as STAU1, thereby preventing degradation
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