Circular RNA circStag1 promotes bone regeneration by interacting with HuR

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Abstract

Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture, leading to an increased risk of fractures. Recently, circular RNAs (circRNAs) have been demonstrated to play pivotal roles in regulating bone metabolism. However, the underlying functions of circRNAs in bone metabolism in postmenopausal osteoporosis remain obscure. Here, we report that circStag1 is a critical osteoporosis-related circRNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells (BMSCs) and clinical bone tissue samples from patients with osteoporosis. Overexpression of circStag1 significantly promoted the osteogenic capability of BMSCs. Mechanistically, we found that circStag1 interacts with human antigen R (HuR), an RNA-binding protein, and promotes the translocation of HuR into the cytoplasm. A high cytoplasmic level of HuR led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6 ( Lrp5/6) and β-catenin expression, thereby stimulating the osteogenic differentiation of BMSCs. Furthermore, overexpression of circStag1 in vivo by circStag1-loaded adeno-associated virus (circStag1-AAV) promoted new bone formation, thereby preventing bone loss in ovariectomized rats. Collectively, we show that circStag1 plays a pivotal role in promoting the regeneration of bone tissue via HuR/Wnt signaling, which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.

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Natural RNA circles function as efficient microRNA sponges.

Thomas B. Hansen, Trine I. Jensen, Bettina H. Clausen … (2014)

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.

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The biogenesis, biology and characterization of circular RNAs

Lasse S. Kristensen, Maria Andersen, Lotte V. W. Stagsted … (2019)

Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.

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The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes.

G van Zundert, J Rodrigues, M Trellet … (2016)

The prediction of the quaternary structure of biomolecular macromolecules is of paramount importance for fundamental understanding of cellular processes and drug design. In the era of integrative structural biology, one way of increasing the accuracy of modeling methods used to predict the structure of biomolecular complexes is to include as much experimental or predictive information as possible in the process. This has been at the core of our information-driven docking approach HADDOCK. We present here the updated version 2.2 of the HADDOCK portal, which offers new features such as support for mixed molecule types, additional experimental restraints and improved protocols, all of this in a user-friendly interface. With well over 6000 registered users and 108,000 jobs served, an increasing fraction of which on grid resources, we hope that this timely upgrade will help the community to solve important biological questions and further advance the field. The HADDOCK2.2 Web server is freely accessible to non-profit users at http://haddock.science.uu.nl/services/HADDOCK2.2.

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Author and article information

Contributors

Dazhi Yang: yangdazhi1111@163.com

Guozhi Xiao:

ORCID: http://orcid.org/0000-0002-4269-2450

xiaogz@sustech.edu.cn

Songlin Peng:

ORCID: http://orcid.org/0000-0002-4042-7071

dyffyy2@mail.sustech.edu.cn

Journal

Journal ID (nlm-ta): Bone Res

Journal ID (iso-abbrev): Bone Res

Title: Bone Research

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-4700

ISSN (Electronic): 2095-6231

Publication date (Electronic): 31 March 2022

Publication date PMC-release: 31 March 2022

Publication date Collection: 2022

Volume: 10

Electronic Location Identifier: 32

Affiliations

[1 ]GRID grid.440218.b, ISNI 0000 0004 1759 7210, Department of Spine Surgery and Institute for Orthopaedic Research, the Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), , Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, ; Shenzhen, 518020 China

[2 ]GRID grid.263817.9, ISNI 0000 0004 1773 1790, The First Affiliated Hospital, , Southern University of Science and Technology, ; Shenzhen, 518055 China

[3 ]GRID grid.258164.c, ISNI 0000 0004 1790 3548, The First Affiliated Hospital, , Jinan University, ; Guangzhou, 510630 China

[4 ]GRID grid.263817.9, ISNI 0000 0004 1773 1790, School of Medicine, , Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, ; Shenzhen, 518055 China

Author information

Guozhi Xiao http://orcid.org/0000-0002-4269-2450

Songlin Peng http://orcid.org/0000-0002-4042-7071

Article

Publisher ID: 208

DOI: 10.1038/s41413-022-00208-x

PMC ID: 8971384

PubMed ID: 35361779

SO-VID: 137855dc-6278-45ae-b28d-64af3d6701ee

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 16 July 2021

Date revision received : 29 January 2022

Date accepted : 28 February 2022

Funding

Funded by: FundRef https://doi.org/10.13039/501100010877, Shenzhen Science and Technology Innovation Commission;

Award ID: JCYJ20180305164659637

Award ID: SGLH20180625141602256

Award ID: JSGG20180504170427135

Award ID: JCYJ20180305164544288

Award ID: JCYJ2017041362104773

Award ID: ZDSYS20200811143752005

Award ID: JCYJ20180305164659637

Award ID: SGLH20180625141602256

Award ID: ZDSYS20200811143752005

Award Recipient : Gaoyang Chen Canling Long Shang Wang Zhenmin Wang Xin Chen Wanze Tang Xiaoqin He Zhiteng Bao Baoyu Tan Jin Zhao Yongheng Xie Zhizhong Li Dazhi Yang Guozhi Xiao Songlin Peng