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.
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Consensus statement
Purpose of this Consensus StatementIn this Consensus Statement we present a current and coherent picture of the roles of lncRNAs in cell and developmental biology, identify the key issues in understanding their functions and chart the path forward. We address lncRNA definition, nomenclature, conservation, expression, phenotypic visibility, functional assays and molecular mechanisms encompassing lncRNA connections to chromatin architecture, epigenetic processes, enhancer function and biomolecular condensates, as well as the roles of lncRNAs outside the nucleus. We argue that loci expressing lncRNAs should be recognized as bona fide genes and discuss lncRNA structure-function relationships as the means to parse mechanisms and pathways. Finally, we identify the current challenges and offer recommendations for understanding the relationship of lncRNAs to genome architecture, gene regulation and cellular organization.The authors of this Consensus Statement were suggested by recommendations of colleagues. Consensus was reached by group e-mail and discussion.
Definition and nomenclature of lncRNAslncRNAs have been arbitrarily defined as non-coding transcripts of more than 200 nucleotides (200 nt), which is a convenient size cutoff in biochemical and biophysical RNA purification protocols that deplete most infrastructural RNAs, such as 5S rRNAs, tRNAs, snRNAs and snoRNAs, as well as miRNAs, siRNAs and piRNAs 23 . This definition also excludes some other well-known short RNAs such as the primatespecific snaRs (~80-120 nt), which associate with nuclear factor 90 (ref. 24); Y ...