A substantial proportion of lncRNAs reside within, or are dynamically shuttled, to the cytoplasm where they regulate protein localization, mRNA translation and stability. For example, the NFAT transcription factor is trafficked from the cytoplasm to the nucleus to activate target genes in response to calcium-dependent signals. A lncRNA, NRON, complexes with importin-β proteins and regulates the trafficking of NFAT113. Notably, NRON inhibits the trafficking of NFAT to the nucleus specifically, with other proteins also trafficked by importin-β proteins, such as NF-κB, being unaffected.
By virtue of their ability to base pair with mRNAs, cytoplasmic lncRNAs also can regulate translation. The UCHL1 mRNA is complemented by an antisense lncRNA, which, in response to stress or the mTOR pathway, is shuttled to the cytoplasm where, via an antisense complementary to the UCHL1 AUG initiation codon and combined inverted SINEB2 domains, increases UCHL1 protein synthesis54.
Additional repeat elements common to lncRNAs and mRNA create a broad interface for complementary interactions. Alu elements in cytoplasmic lncRNA can form imperfect complementary RNA duplexes with Alu elements in the 3′ UTRs of target mRNAs83. Staufen1 subsequently recognizes and binds the resultant dsRNA elements and initiates mRNA decay.
- Mercer TR, Mattick JS (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nature Structural & Molecular Biology 20,300–307(Box 1). [article]