Cytoplasmic functions of long noncoding RNAs

Abstract

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides found throughout the cell that lack protein-coding function. Their functions are closely linked to their interaction with RNA-binding proteins (RBPs) and nucleic acids. Nuclear lncRNAs have been studied extensively, revealing complexes with structural and regulatory roles that enable gene organization and control transcription. Cytoplasmic lncRNAs are less well understood, but accumulating evidence indicates that they also form complexes with diverse structural and regulatory functions. Here, we review our current knowledge of cytoplasmic lncRNAs and the different levels of gene regulation controlled by cytoplasmic lncRNA complexes, including mRNA turnover, translation, protein stability, sponging of cytosolic factors, and modulation of signaling pathways. We conclude by discussing areas of future study needed to elucidate comprehensively the biology of lncRNAs, to further understand the impact of lncRNAs on physiology and design lncRNA-centered therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

Keywords: circRNA; lncRNA; miRNA; noncoding RNA; post-transcriptional gene regulation; ribonucleoprotein complexes.

Figure 1. Different levels of regulation of gene expression by cytoplasmic lncRNAs

(Clockwise). Top, following export to the cytoplasm, lncRNAs can associate with RNA-binding proteins (RBPs) or with partially complementary mRNAs to regulate the stability and/or translation of specific mRNAs. Signaling, association of RBPs with lncRNAs can lead to conformational changes that activate signaling molecules (e.g., kinases). Organelle function, RBPs can chaperone the mobilization of lncRNAs to cellular organelles where they carry out specific functions. Protein stability, lncRNAs can serve as platforms that facilitate the presentation of specific RBPs to the protein degradation machinery. RBP decoy and microRNA decoy, lncRNAs binding to RBPs and microRNAs can reduce the availability of these factors to mRNAs, in turn modulating mRNA fate. See text and Table 1 for details.