Long non-coding RNAs: definitions, functions, challenges and recommendations
John S Mattick 1 2, Paulo P Amaral 3, Piero Carninci 4 5, Susan Carpenter 6, Howard Y Chang 7 8 9 10, Ling-Ling Chen 11, Runsheng Chen 12, Caroline Dean 13, Marcel E Dinger 14 15, Katherine A Fitzgerald 16, Thomas R Gingeras 17, Mitchell Guttman 18, Tetsuro Hirose 19, Maite Huarte 20 21, Rory Johnson 22 23, Chandrasekhar Kanduri 24, Philipp Kapranov 25, Jeanne B Lawrence 26, Jeannie T Lee 27 28, Joshua T Mendell 29 30, Timothy R Mercer 31, Kathryn J Moore 32, Shinichi Nakagawa 33, John L Rinn 34 35 36, David L Spector 17, Igor Ulitsky 37, Yue Wan 38 39, Jeremy E Wilusz 40, Mian Wu 41
Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult.
Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes.
Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates and domains, indicating an intimate link between lncRNA expression and the spatial control of gene expression during development.
lncRNAs also have important roles in the cytoplasm and beyond, including in the regulation of translation, metabolism and signalling. lncRNAs often have a modular structure and are rich in repeats, which are increasingly being shown to be relevant to their function.
In this Consensus Statement, we address the definition and nomenclature of lncRNAs and their conservation, expression, phenotypic visibility, structure and functions. We also discuss research challenges and provide recommendations to advance the understanding of the roles of lncRNAs in development, cell biology and disease.
CITA DEL ARTÍCULO Nat Rev Mol Cell Biol. 2023 Jan 3. DOI: 10.1038/s41580-022-00566-8. Online ahead of print.