New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action
Long non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators that can impact almost all physiological functions. Here, we focus on the long non-coding steroid receptor RNA activator (SRA), including new insights into its effects on gene expression, the cell cycle, and differentiat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2018.00244/full |
| _version_ | 1818141260078120960 |
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| author | Liang Sheng Liang Sheng Lan Ye Dong Zhang William P. Cawthorn Bin Xu |
| author_facet | Liang Sheng Liang Sheng Lan Ye Dong Zhang William P. Cawthorn Bin Xu |
| author_sort | Liang Sheng |
| collection | DOAJ |
| description | Long non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators that can impact almost all physiological functions. Here, we focus on the long non-coding steroid receptor RNA activator (SRA), including new insights into its effects on gene expression, the cell cycle, and differentiation; how these relate to physiology and disease; and the mechanisms underlying these effects. We discuss how SRA acts as an RNA coactivator in nuclear receptor signaling; its effects on steroidogenesis, adipogenesis, and myocyte differentiation; the impact on breast and prostate cancer tumorigenesis; and, finally, its ability to modulate hepatic steatosis through several signaling pathways. Genome-wide analysis reveals that SRA regulates hundreds of target genes in adipocytes and breast cancer cells and binds to thousands of genomic sites in human pluripotent stem cells. Recent studies indicate that SRA acts as a molecular scaffold and forms networks with numerous coregulators and chromatin-modifying regulators in both activating and repressive complexes. We discuss how modifications to SRA's unique stem-loop secondary structure are important for SRA function, and highlight the various SRA isoforms and mutations that have clinical implications. Finally, we discuss the future directions for better understanding the molecular mechanisms of SRA action and how this might lead to new diagnostic and therapeutic approaches. |
| first_indexed | 2024-12-11T10:57:03Z |
| format | Article |
| id | doaj.art-175ea346b6114274a39ef0a54f674afe |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-11T10:57:03Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-175ea346b6114274a39ef0a54f674afe2022-12-22T01:10:01ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2018-09-01510.3389/fmed.2018.00244372724New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of ActionLiang Sheng0Liang Sheng1Lan Ye2Dong Zhang3William P. Cawthorn4Bin Xu5Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, Nanjing, ChinaNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Nanjing, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, ChinaUniversity/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical CenterAnn Arbor, MI, United StatesLong non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators that can impact almost all physiological functions. Here, we focus on the long non-coding steroid receptor RNA activator (SRA), including new insights into its effects on gene expression, the cell cycle, and differentiation; how these relate to physiology and disease; and the mechanisms underlying these effects. We discuss how SRA acts as an RNA coactivator in nuclear receptor signaling; its effects on steroidogenesis, adipogenesis, and myocyte differentiation; the impact on breast and prostate cancer tumorigenesis; and, finally, its ability to modulate hepatic steatosis through several signaling pathways. Genome-wide analysis reveals that SRA regulates hundreds of target genes in adipocytes and breast cancer cells and binds to thousands of genomic sites in human pluripotent stem cells. Recent studies indicate that SRA acts as a molecular scaffold and forms networks with numerous coregulators and chromatin-modifying regulators in both activating and repressive complexes. We discuss how modifications to SRA's unique stem-loop secondary structure are important for SRA function, and highlight the various SRA isoforms and mutations that have clinical implications. Finally, we discuss the future directions for better understanding the molecular mechanisms of SRA action and how this might lead to new diagnostic and therapeutic approaches.https://www.frontiersin.org/article/10.3389/fmed.2018.00244/fulllong non-coding RNA (lncRNA)steroid receptor RNA activator (SRA)physiological functionsregulation of gene expressiondifferentiation |
| spellingShingle | Liang Sheng Liang Sheng Lan Ye Dong Zhang William P. Cawthorn Bin Xu New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action Frontiers in Medicine long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) physiological functions regulation of gene expression differentiation |
| title | New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action |
| title_full | New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action |
| title_fullStr | New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action |
| title_full_unstemmed | New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action |
| title_short | New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action |
| title_sort | new insights into the long non coding rna sra physiological functions and mechanisms of action |
| topic | long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) physiological functions regulation of gene expression differentiation |
| url | https://www.frontiersin.org/article/10.3389/fmed.2018.00244/full |
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