Long non-coding RNAs as emerging regulators of differentiation, development, and disease

Abstract

A significant portion of the mammalian genome encodes numerous transcripts that are not translated into proteins, termed long non-coding RNAs. Initial studies identifying long non-coding RNAs inferred these RNA sequences were a consequence of transcriptional noise or promiscuous RNA polymerase II activity. However, the last decade has seen a revolution in the understanding of regulation and function of long non-coding RNAs. Now it has become apparent that long non-coding RNAs play critical roles in a wide variety of biological processes. In this review, we describe the current understanding of long non-coding RNA-mediated regulation of cellular processes: differentiation, development, and disease.

Keywords: Bvht, braveheart; CDT, C-terminal domain; DBE-T, D4Z4-binding element; DMD, Duchenne muscular dystrophy; ES, embryonic stem; FSHD, facioscapulohumeral muscular dystrophy; Fendrr, Foxf1a called fetal-lethal non-coding developmental regulatory RNA; MEF2, myocyte enhancer factor-2; MRFs, myogenic regulatory factors; Malat1, metastasis associated lung adenocarcinoma transcript 1; Mesp1, mesoderm progenitor 1; Neat2, nuclear-enriched abundant transcript 2; PRC2, polycomb group repressive complex 2; RNAP II, RNA polymerase II; SINE, short interspersed element; SR, serine arginine; SRA, steroid receptor activator; SRY, sex-determining region Y; YAM 1-4, YY1-associated muscle 1-4; ceRNAs, competing endogenous RNAs; ciRS-7, circular RNA sponge for miR-7; development; differentiation; disease; gene expression; iPS, induced pluripotent stem; lncRNAs, long non-coding RNAs; long non-coding RNAs; ncRNAa, non-coding RNA activating; skeletal muscle.

Figure 1.

lncRNAs regulate gene expression using diverse modes of action.

Figure 2.

H19 lncRNA generates miR-675-3p and -5p and promotes skeletal muscle differentiation and regeneration by inhibiting repressors of myogenesis.