Structure and Function of Long Noncoding RNAs in Epigenetic Regulation

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2013 Mar 7

PMID 23463315

Citations 782

Authors

Tim R Mercer

John S Mattick

Affiliations

Soon will be listed here.

Abstract

Genomes of complex organisms encode an abundance and diversity of long noncoding RNAs (lncRNAs) that are expressed throughout the cell and fulfill a wide variety of regulatory roles at almost every stage of gene expression. These roles, which encompass sensory, guiding, scaffolding and allosteric capacities, derive from folded modular domains in lncRNAs. In this diverse functional repertoire, we focus on the well-characterized ability for lncRNAs to function as epigenetic modulators. Many lncRNAs bind to chromatin-modifying proteins and recruit their catalytic activity to specific sites in the genome, thereby modulating chromatin states and impacting gene expression. Considering this regulatory potential in combination with the abundance of lncRNAs suggests that lncRNAs may be part of a broad epigenetic regulatory network.

Citing Articles

m6A-modified LINC02418 induces transcriptional and post-transcriptional modification of CTNNB1 via interacting with YBX1 and IGF2BP1 in colorectal cancer.

Zhang H, Han Y, Wu C, Wang S, Chen M, Xu Q Cell Death Discov. 2025; 11(1):101.

PMID: 40082414 PMC: 11906587. DOI: 10.1038/s41420-025-02365-4.

The human genome encodes a multitude of novel miRNAs.

Gao F, Wang F, Chen Y, Deng B, Yang F, Cao H Nucleic Acids Res. 2025; 53(4).

PMID: 39964476 PMC: 11833695. DOI: 10.1093/nar/gkaf070.

Long non-coding RNA NEAT1 promotes colorectal cancer progression via interacting with SIRT1.

Li Y, Xu Y, Yu X, Su S, Wu B, Su Y Sci Rep. 2025; 15(1):5673.

PMID: 39955367 PMC: 11830096. DOI: 10.1038/s41598-025-90416-2.

mRNA Transcript Variants Expressed in Mammalian Cells.

Sharma Y, Vo K, Shila S, Paul A, Dahiya V, Fields P Int J Mol Sci. 2025; 26(3).

PMID: 39940824 PMC: 11817330. DOI: 10.3390/ijms26031052.

A novel lncRNA enhances autophagy to suppress extracellular matrix via modulating TP53INP1 in human trabecular meshwork cells under oxidative stress.

Tie J, Guo J, Huang Y, Huang Z, Yan Z, Yuan J Sci Rep. 2025; 15(1):5049.

PMID: 39934637 PMC: 11814328. DOI: 10.1038/s41598-024-81300-6.

References

Ohhata T, Hoki Y, Sasaki H, Sado T . Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification. Development. 2007; 135(2):227-35. DOI: 10.1242/dev.008490. View

Lunde B, Moore C, Varani G . RNA-binding proteins: modular design for efficient function. Nat Rev Mol Cell Biol. 2007; 8(6):479-90. PMC: 5507177. DOI: 10.1038/nrm2178. View

Novikova I, Hennelly S, Sanbonmatsu K . Structural architecture of the human long non-coding RNA, steroid receptor RNA activator. Nucleic Acids Res. 2012; 40(11):5034-51. PMC: 3367176. DOI: 10.1093/nar/gks071. View

Yap K, Li S, Munoz-Cabello A, Raguz S, Zeng L, Mujtaba S . Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010; 38(5):662-74. PMC: 2886305. DOI: 10.1016/j.molcel.2010.03.021. View

Nagano T, Mitchell J, Sanz L, Pauler F, Ferguson-Smith A, Feil R . The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science. 2008; 322(5908):1717-20. DOI: 10.1126/science.1163802. View

Squires J, Patel H, Nousch M, Sibbritt T, Humphreys D, Parker B . Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 2012; 40(11):5023-33. PMC: 3367185. DOI: 10.1093/nar/gks144. View

Lescoute A, Westhof E . The interaction networks of structured RNAs. Nucleic Acids Res. 2006; 34(22):6587-604. PMC: 1747187. DOI: 10.1093/nar/gkl963. View

Cabili M, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A . Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011; 25(18):1915-27. PMC: 3185964. DOI: 10.1101/gad.17446611. View

Win M, Smolke C . Higher-order cellular information processing with synthetic RNA devices. Science. 2008; 322(5900):456-60. PMC: 2805114. DOI: 10.1126/science.1160311. View

10.

Maison C, Bailly D, Roche D, Montes de Oca R, Probst A, Vassias I . SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin. Nat Genet. 2011; 43(3):220-7. DOI: 10.1038/ng.765. View

11.

Jorg T, Martin O, Wagner A . Neutral network sizes of biological RNA molecules can be computed and are not atypically small. BMC Bioinformatics. 2008; 9:464. PMC: 2639431. DOI: 10.1186/1471-2105-9-464. View

12.

Djupedal I, Ekwall K . Epigenetics: heterochromatin meets RNAi. Cell Res. 2009; 19(3):282-95. DOI: 10.1038/cr.2009.13. View

13.

Hasegawa Y, Brockdorff N, Kawano S, Tsutui K, Tsutui K, Nakagawa S . The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Dev Cell. 2010; 19(3):469-76. DOI: 10.1016/j.devcel.2010.08.006. View

14.

Khalil A, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D . Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009; 106(28):11667-72. PMC: 2704857. DOI: 10.1073/pnas.0904715106. View

15.

Ferrada E, Wagner A . A comparison of genotype-phenotype maps for RNA and proteins. Biophys J. 2012; 102(8):1916-25. PMC: 3328697. DOI: 10.1016/j.bpj.2012.01.047. View

16.

Hogan D, Riordan D, Gerber A, Herschlag D, Brown P . Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system. PLoS Biol. 2008; 6(10):e255. PMC: 2573929. DOI: 10.1371/journal.pbio.0060255. View

17.

Wagner A . The role of robustness in phenotypic adaptation and innovation. Proc Biol Sci. 2012; 279(1732):1249-58. PMC: 3282381. DOI: 10.1098/rspb.2011.2293. View

18.

Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M . Antisense transcription in the mammalian transcriptome. Science. 2005; 309(5740):1564-6. DOI: 10.1126/science.1112009. View

19.

Mattick J . The genetic signatures of noncoding RNAs. PLoS Genet. 2009; 5(4):e1000459. PMC: 2667263. DOI: 10.1371/journal.pgen.1000459. View

20.

Yomo T, Prijambada I, Yamamoto K, Shima Y, Negoro S, Urabe I . Properties of artificial proteins with random sequences. Ann N Y Acad Sci. 1999; 864:131-5. DOI: 10.1111/j.1749-6632.1998.tb10295.x. View