Recent studies have revealed the regulatory potential of many long noncoding RNAs (lncRNAs). Most lncRNAs, like mRNAs, are transcribed by RNA polymerase II and are capped, polyadenylated, and spliced. However, the subcellular fates of lncRNAs are distinct and the mechanisms of action are diverse. Investigating the mechanisms that determine the subcellular fate of lncRNAs has the potential to provide new insights into their biogenesis and specialized functions.
- Long noncoding RNAs (lncRNAs) comprise different classes of RNA molecules with sizes greater than 200 nt.
- The function of lncRNAs is associated with their unique subcellular localization patterns.
- Mature lncRNAs can accumulate in cis, localize in the nucleus in trans, or export to the cytoplasm to execute their functions.
- Multiple factors including ribonucleic nuclear retention elements, nuclear protein factors, higher-order chromosome organization, and the coupling of RNA–protein assemblies with lncRNA transcription may dictate the subcellular localization patterns of lncRNAs.
- A better understanding of the lncRNAs themselves is crucial to link these noncoding transcripts to RNA biology and to address their cellular roles in depth.
Functions of Long Noncoding RNAs (lncRNAs) Are Associated with Their Subcellular Fates. lncRNAs have distinct subcellular localization patterns, allowing lncRNAs to execute their specified functions.
(A) lncRNAs can accumulate and act in cis once they are transcribed. (B) lncRNAs can accumulate in cis once they are transcribed, but act in trans that affects genes located in the same chromosome at a distance or in different chromosomes. (A and B) Mechanisms of lncRNA in cis localization are largely unknown. (C) lncRNAs can localize to elsewhere in the nucleoplasm in trans and act in trans. (D) lncRNAs can accumulate to specific nuclear bodies (orange circles) and act in trans. The mechanisms of lncRNA nuclear retention remain largely unknown, as does whether such lncRNAs are required to be translocated in the nucleus to regulate gene expression. (E) lncRNAs can be exported to the cytoplasm to execute their functions. For example, a cytoplasmic lncRNA can sequester protein (pink circle) or interfere with protein post-translational modification (PTM). Whether the nucleocytoplasmic export of cytoplasmic lncRNAs is distinct from that of mRNA has not yet been examined.