LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation

Abstract

Biomolecules specifically aggregate in the cytoplasm and nucleus, driving liquid-liquid phase separation (LLPS) formation and diverse biological processes. Extensive studies have focused on revealing multiple functional membraneless organelles in both the nucleus and cytoplasm. Condensation compositions of LLPS, such as proteins and RNAs affecting the formation of phase separation, have been gradually unveiled. LncRNAs possessing abundant second structures usually promote phase separation formation by providing architectural scaffolds for diverse RNAs and proteins interaction in both the nucleus and cytoplasm. Beyond scaffolds, lncRNAs may possess more diverse functions, such as functioning as enhancer RNAs or buffers. In this review, we summarized current studies on the function of phase separation and its related lncRNAs, mainly in the nucleus. This review will facilitate our understanding of the formation and function of phase separation and the role of lncRNAs in these processes and related biological activities. A deeper understanding of the formation and maintaining of phase separation will be beneficial for disease diagnosis and treatment.

Keywords: lncRNAs; nuclear bodies; phase separation; signaling transduction; therapeutics treatments.

FIGURE 1

The graphical abstract of phase-separation related LncRNAs involved in cellular function. (A) LncRNA NORAD functions as a multivalent binding platform for PUM1/2 proteins in cytoplasm; (B) LncRNA Xist mediates X chromosome silence and subsequently drives interaction between inactivated X chromosome and Lamin-B receptor (LBR); (C) LncRNA PNCTR sequesters PTBP1 in the perinucleolar compartment (PNC) and modulates splicing regulation function of PTBP1 protein; (D) DilncRNA synthesized at DSB foci and coordinates DDR proteins to promote the formation of DDR foci to response to DBS; (E) LncRNA NEAT1 functions as scaffolds to recruit CARM1, PSPC1, and p54nrb proteins to regulate cell differentiation and embryo development in paraspeckle; (F) LncRNA TNBL is accumulated as a perinucleolar aggregate at NBL2 loci and close to SAM68 body and is involved in genome organization, splicing regulation, and mRNA stability, respectively; (G) LncRNA HSATIII is involved in two nuclear bodies, n SB-M and n SB-S, formation to respond to thermal stress.