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      LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation

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          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.

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          Most cited references133

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          Biomolecular condensates: organizers of cellular biochemistry

          In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge.
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            Long Noncoding RNAs in Cancer Pathways.

            Genome-wide cancer mutation analyses are revealing an extensive landscape of functional mutations within the noncoding genome, with profound effects on the expression of long noncoding RNAs (lncRNAs). While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, we now understand that lncRNAs drive many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein, and RNA. Recent advancements in surveying lncRNA molecular mechanisms are now providing the tools to functionally annotate these cancer-associated transcripts, making these molecules attractive targets for therapeutic intervention in the fight against cancer.
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              Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates

              Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells. This realization has motivated major efforts to delineate the function of such biomolecular condensates in normal cells and their roles in contexts ranging from development to age-related disease. There is great interest in understanding the underlying biophysical principles and the specific properties of biological condensates with the goal of bringing insights into a wide range of biological processes and systems. The explosion of physiological and pathological contexts involving LLPS requires clear standards for their study. Here, we propose guidelines for rigorous experimental characterization of LLPS processes in vitro and in cells, discuss the caveats of common experimental approaches, and point out experimental and theoretical gaps in the field.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                31 March 2021
                2021
                : 12
                : 626234
                Affiliations
                [1] 1Department of Obstetrics and Gynecology, Women’s Hospital, School of Medicine, Zhejiang University , Hangzhou, China
                [2] 2College of Life Sciences, Zhejiang University , Hangzhou, China
                [3] 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China
                [4] 4Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University , Haining, China
                [5] 5Breast Center of The First Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou, China
                Author notes

                Edited by: Xiao Li, Texas Heart Institute, United States

                Reviewed by: Bo Wen, Fudan University, China; Xianghui Fu, Sichuan University, China

                *Correspondence: Jun Lin, linjun@ 123456zju.edu.cn

                This article was submitted to RNA, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2021.626234
                8044363
                33868368
                702e9804-fc2a-4e12-9303-6a6fda90323e
                Copyright © 2021 Luo, Qu, Gao, Lin, Liu and Lin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 November 2020
                : 25 February 2021
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 133, Pages: 13, Words: 0
                Categories
                Genetics
                Review

                Genetics
                phase separation,lncrnas,nuclear bodies,signaling transduction,therapeutics treatments
                Genetics
                phase separation, lncrnas, nuclear bodies, signaling transduction, therapeutics treatments

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