Developmental Dynamics of LncRNAs Across Mammalian Organs and Species

Overview

Journal Nature

Specialty Science

Date 2019 Jun 28

PMID 31243368

Citations 155

Authors

Ioannis Sarropoulos

Ray Marin

Margarida Cardoso-Moreira

Henrik Kaessmann

Affiliations

Soon will be listed here.

Abstract

Although many long noncoding RNAs (lncRNAs) have been identified in human and other mammalian genomes, there has been limited systematic functional characterization of these elements. In particular, the contribution of lncRNAs to organ development remains largely unexplored. Here we analyse the expression patterns of lncRNAs across developmental time points in seven major organs, from early organogenesis to adulthood, in seven species (human, rhesus macaque, mouse, rat, rabbit, opossum and chicken). Our analyses identified approximately 15,000 to 35,000 candidate lncRNAs in each species, most of which show species specificity. We characterized the expression patterns of lncRNAs across developmental stages, and found many with dynamic expression patterns across time that show signatures of enrichment for functionality. During development, there is a transition from broadly expressed and conserved lncRNAs towards an increasing number of lineage- and organ-specific lncRNAs. Our study provides a resource of candidate lncRNAs and their patterns of expression and evolutionary conservation across mammalian organ development.

Citing Articles

Unravelling the Regulatory Roles of lncRNAs in Melanoma: From Mechanistic Insights to Target Selection.

Moras B, Sissi C Int J Mol Sci. 2025; 26(5).

PMID: 40076754 PMC: 11900516. DOI: 10.3390/ijms26052126.

The diagnostic and prognostic significance of HOXC13-AS and its molecular regulatory mechanism in human cancer.

Gu X, Hu X, Zhang S, Zhang X, Wang Y, Li L Front Mol Biosci. 2025; 12:1540048.

PMID: 39981436 PMC: 11839424. DOI: 10.3389/fmolb.2025.1540048.

lncRNA NORAD modulates STAT3/STAT1 balance and innate immune responses in human cells via interaction with STAT3.

Argoetti A, Shalev D, Polyak G, Shima N, Biran H, Lahav T Nat Commun. 2025; 16(1):571.

PMID: 39794357 PMC: 11723954. DOI: 10.1038/s41467-025-55822-0.

Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells.

Chen Y, Sha W, Zhang Y, Kou W, Yang L, Guo R Open Med (Wars). 2024; 19(1):20241073.

PMID: 39588384 PMC: 11587921. DOI: 10.1515/med-2024-1073.

Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells.

Liang W, Muller S, Hart S, Wessels H, Mendez-Mancilla A, Sookdeo A Cell. 2024; 187(26):7637-7654.e29.

PMID: 39532094 PMC: 11682925. DOI: 10.1016/j.cell.2024.10.021.

References

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

Gregg J . Codes, conscience and conflicts: ethical dilemmas in midwifery practice. Midwives Chron. 1987; 100(1199):392-5. View

Iyer M, Niknafs Y, Malik R, Singhal U, Sahu A, Hosono Y . The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015; 47(3):199-208. PMC: 4417758. DOI: 10.1038/ng.3192. View

Hon C, Ramilowski J, Harshbarger J, Bertin N, Rackham O, Gough J . An atlas of human long non-coding RNAs with accurate 5' ends. Nature. 2017; 543(7644):199-204. PMC: 6857182. DOI: 10.1038/nature21374. View

Carninci P, Kasukawa T, Katayama S, Gough J, Frith M, Maeda N . The transcriptional landscape of the mammalian genome. Science. 2005; 309(5740):1559-63. DOI: 10.1126/science.1112014. View

Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U . The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature. 2014; 505(7485):635-40. DOI: 10.1038/nature12943. View

Washietl S, Kellis M, Garber M . Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals. Genome Res. 2014; 24(4):616-28. PMC: 3975061. DOI: 10.1101/gr.165035.113. View

Hezroni H, Koppstein D, Schwartz M, Avrutin A, Bartel D, Ulitsky I . Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Rep. 2015; 11(7):1110-22. PMC: 4576741. DOI: 10.1016/j.celrep.2015.04.023. View

Kopp F, Mendell J . Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell. 2018; 172(3):393-407. PMC: 5978744. DOI: 10.1016/j.cell.2018.01.011. View

10.

Ponting C, Oliver P, Reik W . Evolution and functions of long noncoding RNAs. Cell. 2009; 136(4):629-41. DOI: 10.1016/j.cell.2009.02.006. View

11.

Ulitsky I . Evolution to the rescue: using comparative genomics to understand long non-coding RNAs. Nat Rev Genet. 2016; 17(10):601-14. DOI: 10.1038/nrg.2016.85. View

12.

Necsulea A, Kaessmann H . Evolutionary dynamics of coding and non-coding transcriptomes. Nat Rev Genet. 2014; 15(11):734-48. DOI: 10.1038/nrg3802. View

13.

Guttman M, Amit I, Garber M, French C, Lin M, Feldser D . Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009; 458(7235):223-7. PMC: 2754849. DOI: 10.1038/nature07672. View

14.

Ulitsky I, Shkumatava A, Jan C, Sive H, Bartel D . Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell. 2011; 147(7):1537-50. PMC: 3376356. DOI: 10.1016/j.cell.2011.11.055. View

15.

Sauvageau M, Goff L, Lodato S, Bonev B, Groff A, Gerhardinger C . Multiple knockout mouse models reveal lincRNAs are required for life and brain development. Elife. 2014; 2:e01749. PMC: 3874104. DOI: 10.7554/eLife.01749. View

16.

Grote P, Herrmann B . Long noncoding RNAs in organogenesis: making the difference. Trends Genet. 2015; 31(6):329-35. DOI: 10.1016/j.tig.2015.02.002. View

17.

Goff L, Groff A, Sauvageau M, Trayes-Gibson Z, Sanchez-Gomez D, Morse M . Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A. 2015; 112(22):6855-62. PMC: 4460505. DOI: 10.1073/pnas.1411263112. View

18.

Zerbino D, Achuthan P, Akanni W, Amode M, Barrell D, Bhai J . Ensembl 2018. Nucleic Acids Res. 2017; 46(D1):D754-D761. PMC: 5753206. DOI: 10.1093/nar/gkx1098. View

19.

Conesa A, Nueda M, Ferrer A, Talon M . maSigPro: a method to identify significantly differential expression profiles in time-course microarray experiments. Bioinformatics. 2006; 22(9):1096-102. DOI: 10.1093/bioinformatics/btl056. View

20.

Mukherjee N, Calviello L, Hirsekorn A, de Pretis S, Pelizzola M, Ohler U . Integrative classification of human coding and noncoding genes through RNA metabolism profiles. Nat Struct Mol Biol. 2016; 24(1):86-96. DOI: 10.1038/nsmb.3325. View