Review

. 2021 Dec;1506(1):118-141.

doi: 10.1111/nyas.14713. Epub 2021 Nov 17.

Noncoding RNAs: biology and applications-a Keystone Symposia report

Jennifer Cable¹, Edith Heard^{2

3}, Tetsuro Hirose^{4

5}, Kannanganattu V Prasanth⁶, Ling-Ling Chen^{7

8

9}, Jonathan E Henninger¹⁰, Sofia A Quinodoz¹¹, David L Spector¹², Sarah D Diermeier¹³, Allison M Porman¹⁴, Dhiraj Kumar¹⁵, Mark W Feinberg¹⁶, Xiaohua Shen¹⁷, Juan Pablo Unfried¹⁸, Rory Johnson^{19

20}, Chun-Kan Chen^{21

22}, Jeremy E Wilusz²³, Adelheid Lempradl²⁴, Sean E McGeary^{10

25}, Lamia Wahba^{22

26}, Anna Marie Pyle^{27

28}, Amanda E Hargrove²⁹, Matthew D Simon³⁰, Marco Marcia³¹, Róża K Przanowska³², Howard Y Chang^{21

33}, Samie R Jaffrey³⁴, Lydia M Contreras³⁵, Qi Chen³⁶, Junchao Shi³⁶, Joshua T Mendell³⁷, Lin He³⁸, Erwei Song³⁹, John L Rinn⁴⁰, Mukesh Kumar Lalwani⁴¹, Murat Can Kalem⁴², Edward B Chuong⁴³, Lynne E Maquat⁴⁴, Xuhang Liu⁴⁵

Affiliations

¹ PhD Science Writer, New York, New York.
² European Molecular Biology Laboratory (EMBL), Heidelberg, Heidelberg, Germany.
³ Collège de France, Paris, France.
⁴ Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
⁵ Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
⁶ Department of Cell and Developmental Biology, Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois.
⁷ State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Shanghai, China.
⁸ School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
⁹ School of Life Sciences, Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences, Hangzhou, China.
¹⁰ Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
¹¹ Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey.
¹² Cold Spring Harbor Laboratory, Cold Spring Harbor and Genetics Program, Stony Brook University, Stony Brook, New York.
¹³ Department of Biochemistry, University of Otago, Dunedin, New Zealand.
¹⁴ Biochemistry and Molecular Genetics Department, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
¹⁵ Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁶ Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
¹⁷ Tsinghua-Peking Joint Center for Life Sciences, School of Medicine and School of Life Sciences, Tsinghua University, Beijing, China.
¹⁸ Center for Applied Medical Research (CIMA), Department of Gene Therapy and Regulation of Gene Expression, Universidad de Navarra (UNAV), Pamplona, Spain.
¹⁹ Department of Medical Oncology, Inselspital, Bern University Hospital; and Department for BioMedical Research University of Bern, Bern, Switzerland.
²⁰ School of Biology and Environmental Science and Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
²¹ Center for Personal Dynamic Regulomes, Stanford University, Stanford, California.
²² Department of Genetics, Stanford University School of Medicine, Stanford, California.
²³ Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
²⁴ Department of Metabolism and Nutritional Programming, Van Andel Research Institute, Grand Rapids, Michigan.
²⁵ Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
²⁶ Department of Pathology, Stanford University School of Medicine, Stanford, California.
²⁷ Department of Genetics, Yale School of Medicine, New Haven, Connecticut.
²⁸ Connecticut and Howard Hughes Medical Institute, Chevy Chase, Maryland.
²⁹ Department of Chemistry, Duke University, Durham, North Carolina.
³⁰ Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut.
³¹ European Molecular Biology Laboratory (EMBL) Grenoble, Grenoble, France.
³² Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia.
³³ Howard Hughes Medical Institute, Stanford University, Stanford, California.
³⁴ Department of Pharmacology, Weill Medical College of Cornell University, New York, New York.
³⁵ McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, Texas.
³⁶ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, California.
³⁷ Department of Molecular Biology, Harold C. Simmons Comprehensive Cancer Center, Hamon Center for Regenerative Science and Medicine; and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas.
³⁸ Division of Cellular and Developmental Biology, Molecular and Cell Biology Department, University of California at Berkeley, Berkeley, California.
³⁹ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center and Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Bioland Laboratory; Program of Molecular Medicine, Zhongshan School of Medicine, Sun Yat-sen University; and Fountain-Valley Institute for Life Sciences, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences Guangzhou, Guangzhou, China.
⁴⁰ Department of Biochemistry, BioFrontiers Institute, and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado.
⁴¹ Queens Medical Research Institute, BHF Centre for Cardiovascular Sciences, University of Edinburgh, Scotland, United Kingdom.
⁴² Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, New York.
⁴³ Department of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado.
⁴⁴ Department of Biochemistry and Biophysics, School of Medicine and Dentistry and Center for RNA Biology, University of Rochester, Rochester, New York.
⁴⁵ Laboratory of Systems Cancer Biology, The Rockefeller University, New York, New York.

PMID: 34791665
PMCID: PMC9808899
DOI: 10.1111/nyas.14713

Review

Noncoding RNAs: biology and applications-a Keystone Symposia report

Jennifer Cable et al. Ann N Y Acad Sci. 2021 Dec.

. 2021 Dec;1506(1):118-141.

doi: 10.1111/nyas.14713. Epub 2021 Nov 17.

Authors

Affiliations

¹ PhD Science Writer, New York, New York.
² European Molecular Biology Laboratory (EMBL), Heidelberg, Heidelberg, Germany.
³ Collège de France, Paris, France.
⁴ Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
⁵ Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
⁶ Department of Cell and Developmental Biology, Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois.
⁷ State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Shanghai, China.
⁸ School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
⁹ School of Life Sciences, Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences, Hangzhou, China.
¹⁰ Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
¹¹ Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey.
¹² Cold Spring Harbor Laboratory, Cold Spring Harbor and Genetics Program, Stony Brook University, Stony Brook, New York.
¹³ Department of Biochemistry, University of Otago, Dunedin, New Zealand.
¹⁴ Biochemistry and Molecular Genetics Department, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
¹⁵ Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁶ Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
¹⁷ Tsinghua-Peking Joint Center for Life Sciences, School of Medicine and School of Life Sciences, Tsinghua University, Beijing, China.
¹⁸ Center for Applied Medical Research (CIMA), Department of Gene Therapy and Regulation of Gene Expression, Universidad de Navarra (UNAV), Pamplona, Spain.
¹⁹ Department of Medical Oncology, Inselspital, Bern University Hospital; and Department for BioMedical Research University of Bern, Bern, Switzerland.
²⁰ School of Biology and Environmental Science and Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
²¹ Center for Personal Dynamic Regulomes, Stanford University, Stanford, California.
²² Department of Genetics, Stanford University School of Medicine, Stanford, California.
²³ Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
²⁴ Department of Metabolism and Nutritional Programming, Van Andel Research Institute, Grand Rapids, Michigan.
²⁵ Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
²⁶ Department of Pathology, Stanford University School of Medicine, Stanford, California.
²⁷ Department of Genetics, Yale School of Medicine, New Haven, Connecticut.
²⁸ Connecticut and Howard Hughes Medical Institute, Chevy Chase, Maryland.
²⁹ Department of Chemistry, Duke University, Durham, North Carolina.
³⁰ Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut.
³¹ European Molecular Biology Laboratory (EMBL) Grenoble, Grenoble, France.
³² Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia.
³³ Howard Hughes Medical Institute, Stanford University, Stanford, California.
³⁴ Department of Pharmacology, Weill Medical College of Cornell University, New York, New York.
³⁵ McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, Texas.
³⁶ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, California.
³⁷ Department of Molecular Biology, Harold C. Simmons Comprehensive Cancer Center, Hamon Center for Regenerative Science and Medicine; and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas.
³⁸ Division of Cellular and Developmental Biology, Molecular and Cell Biology Department, University of California at Berkeley, Berkeley, California.
³⁹ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center and Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Bioland Laboratory; Program of Molecular Medicine, Zhongshan School of Medicine, Sun Yat-sen University; and Fountain-Valley Institute for Life Sciences, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences Guangzhou, Guangzhou, China.
⁴⁰ Department of Biochemistry, BioFrontiers Institute, and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado.
⁴¹ Queens Medical Research Institute, BHF Centre for Cardiovascular Sciences, University of Edinburgh, Scotland, United Kingdom.
⁴² Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, New York.
⁴³ Department of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado.
⁴⁴ Department of Biochemistry and Biophysics, School of Medicine and Dentistry and Center for RNA Biology, University of Rochester, Rochester, New York.
⁴⁵ Laboratory of Systems Cancer Biology, The Rockefeller University, New York, New York.

PMID: 34791665
PMCID: PMC9808899
DOI: 10.1111/nyas.14713

Erratum in

Erratum for.
[No authors listed] [No authors listed] Ann N Y Acad Sci. 2022 Jan;1507(1):171. doi: 10.1111/nyas.14751. Ann N Y Acad Sci. 2022. PMID: 35061911 No abstract available.

Abstract

The human transcriptome contains many types of noncoding RNAs, which rival the number of protein-coding species. From long noncoding RNAs (lncRNAs) that are over 200 nucleotides long to piwi-interacting RNAs (piRNAs) of only 20 nucleotides, noncoding RNAs play important roles in regulating transcription, epigenetic modifications, translation, and cell signaling. Roles for noncoding RNAs in disease mechanisms are also being uncovered, and several species have been identified as potential drug targets. On May 11-14, 2021, the Keystone eSymposium "Noncoding RNAs: Biology and Applications" brought together researchers working in RNA biology, structure, and technologies to accelerate both the understanding of RNA basic biology and the translation of those findings into clinical applications.

Keywords: Xist; circRNA; lncRNA; noncoding RNA; nuclear condensate; phase transition; piRNA; transcription.

PubMed Disclaimer

Figures

**Figure 1.**
HSATIII arcRNAs form nSBs upon thermal stress that sequester proteins involved in intron splicing, including SRSF and SAFB. Upon recovery from thermal stress, additional factors are recruited to the nSBs, including CLK1.

**Figure 2.**
An m6A modification site in HOTAIR required for HOTAIR-mediated cell proliferation and invasion in breast cancer cells.

**Figure 3.**
Proposed mechanism of lncRNA SNHG12 regulation of atherosclerosis through a DNA-PK-mediated DNA damage response in the vascular endothelium.

**Figure 4.**
IRES sequences identify potential protein-coding circRNAs.

**Figure 5.**
An invariant loop within domain 2 (D2) of MEG3 required for p53 activation mediated by MEG3.

**Figure 6.**
Tornado generates circRNA species that are highly stable and expressed at high levels in mammalian cells.

**Figure 7.**
Models of understanding regional RNA accessibility and interfaces available for binding interactions that may play roles in regulatory processes.

**Figure 8.**
Interactions between nucleolin and 5′-tRFCys enhances nucleolin binding to a subset of transcripts, including several metabolic enzymes, and enhances their expression.

See this image and copyright information in PMC

References

1. Chowdhary A, Satagopam V. & Schneider R. 2021. Long Non-coding RNAs: Mechanisms, Experimental, and Computational Approaches in Identification, Characterization, and Their Biomarker Potential in Cancer. Front. Genet 12: 649619. - PMC - PubMed
1. Mattick JS & Makunin IV 2006. Non-coding RNA. Hum. Mol. Genet 15 Spec No 1: R17–29. - PubMed
1. Dossin F. & Heard E. 2021. The Molecular and Nuclear Dynamics of X-Chromosome Inactivation. Cold Spring Harb. Perspect. Biol a040196. - PMC - PubMed
1. Engreitz JM, Pandya-Jones A, McDonel P, et al. 2013. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341: 1237973. - PMC - PubMed
1. Giorgetti L, Lajoie BR, Carter AC, et al. 2016. Structural organization of the inactive X chromosome in the mouse. Nature 535: 575–579. - PMC - PubMed

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Noncoding RNAs: biology and applications-a Keystone Symposia report

Affiliations

Noncoding RNAs: biology and applications-a Keystone Symposia report

Authors

Affiliations

Erratum in

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources