Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 31:12:626234.
doi: 10.3389/fgene.2021.626234. eCollection 2021.

LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation

Jie Luo  1 , Lei Qu  2 , Feiran Gao  3   4 , Jun Lin  1 , Jian Liu  3   4 , Aifu Lin  2   5
Affiliations
Review

LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation

Jie Luo et al. Front Genet. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
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.
See this image and copyright information in PMC

References

    1. Adriaens C., Standaert L., Barra J., Latil M., Verfaillie A., Kalev P., et al. (2016). p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. Nat. Med. 22 861–868. 10.1038/nm.4135 - DOI - PubMed
    1. Alberti S., Gladfelter A., Mittag T. (2019). Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell 176 419–434. 10.1016/j.cell.2018.12.035 - DOI - PMC - PubMed
    1. Aly M. K., Ninomiya K., Adachi S., Natsume T., Hirose T. (2019). Two distinct nuclear stress bodies containing different sets of RNA-binding proteins are formed with HSATIII architectural noncoding RNAs upon thermal stress exposure. Biochem. Biophys. Res. Commun. 516 419–423. 10.1016/j.bbrc.2019.06.061 - DOI - PubMed
    1. Anderson D. M., Anderson K. M., Chang C. L., Makarewich C. A., Nelson B. R., McAnally J. R. (2015). A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160 595–606. 10.1016/j.cell.2015.01.009 - DOI - PMC - PubMed
    1. Arora R., Lee Y., Wischnewski H., Brun C. M., Schwarz T., Azzalin C. M. (2014). RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells. Nat. Commun. 5:5220. - PMC - PubMed

LinkOut - more resources