Naming 'junk': Human non-protein coding RNA (ncRNA) gene nomenclature

Abstract

Previously, the majority of the human genome was thought to be 'junk' DNA with no functional purpose. Over the past decade, the field of RNA research has rapidly expanded, with a concomitant increase in the number of non-protein coding RNA (ncRNA) genes identified in this 'junk'. Many of the encoded ncRNAs have already been shown to be essential for a variety of vital functions, and this wealth of annotated human ncRNAs requires standardised naming in order to aid effective communication. The HUGO Gene Nomenclature Committee (HGNC) is the only organisation authorised to assign standardised nomenclature to human genes. Of the 30,000 approved gene symbols currently listed in the HGNC database (http://www.genenames.org/search), the majority represent protein-coding genes; however, they also include pseudogenes, phenotypic loci and some genomic features. In recent years the list has also increased to include almost 3,000 named human ncRNA genes. HGNC is actively engaging with the RNA research community in order to provide unique symbols and names for each sequence that encodes an ncRNA. Most of the classical small ncRNA genes have now been provided with a unique nomenclature, and work on naming the long (> 200 nucleotides) non-coding RNAs (lncRNAs) is ongoing.

that, in the majority of cases, do not share sequence homology with each other. These longer transcripts are spliced, capped and polyadenylated, suggesting that they are expressed and potentially functional within cells. Indeed, some lncRNAs do now have proven functions, and where these are known they have been named accordingly; for instance, 'XIST' 'X (inactive)-specific transcript (non-protein coding)' is involved in transcriptionally silencing one of the pair of X chromosomes [33]. There are, however, potentially thousands of lncRNAs, and for the vast majority their function remains unresolved. Where lncRNAs reside on the opposite strand to a protein-coding gene, it is thought that they could potentially regulate the expression of the coding gene [34]. These antisense transcripts are named using the approved HGNC symbol for the protein-coding gene with the suffix '-AS' for 'antisense'; the lncRNA gene on the opposite strand to the BOK gene is 'BOK-AS1' for 'BOK antisense RNA 1 (non-protein coding)'. Likewise, those lncRNA genes that reside entirely within an intron of a protein-coding gene are symbolised by the suffix '-IT' for 'intronic transcript' (eg 'MAGI2-IT1' for 'MAGI2 intronic transcript 1 (non-protein coding)'). There are also lncRNAs that are postulated to function only as transcriptional apparatus for the expression of small ncRNA genes nested within their introns. These 'host genes' are named with the suffix 'HG' (eg 'SNHG1' for 'small nucleolar RNA host gene 1 (non-protein coding)'). A small number of lncRNAs share homology with each other and are named as paralogues (eg TTTY1A and TTTY1B). Many transcripts do not fit any of these scenarios, that is: the function of the mature transcript is unknown; they are not proximal to a protein-coding gene; and they are not a member of a homologous family. Such 'orphan' ncRNA genes were previously all named with the anonymous stem symbol NCRNA# (eg 'NCRNA00029') but, in collaboration with the lncRNA database lncRNAdb (http://www.lncrnadb.org)[35] and the Vertebrate Genome Annotation (VEGA; http://vega.sanger.ac.uk/) team,[36] HGNC has recently decided to name these intergenic lncRNA genes with the symbol 'LINC#' for 'long intergenic non-protein coding RNA #'.

RNA nomenclature across species

Where an equivalent orthologous ncRNA gene can be shown to exist in another species, the human RNA gene nomenclature could be transferred directly to the other species and, indeed, this is already happening for highly conserved classes of small RNAs, such as the microRNAs. For example, mouse Mir100 is orthologous to human MIR100. The nomenclature for other ncRNA classes that have greatly diverged across genomes will need careful annotation and may require species-specific nomenclature.

Conclusion

Recent years have shown us that the human genome does not comprise transcriptional deserts of 'junk' DNA lying between protein-coding genes, but rather that these regions encode thousands of transcribed ncRNAs that may play crucial roles in vital biological processes. As a result, interest in these RNAs is growing quickly, and HGNC aims to keep apace with the discovery of new ncRNA classes to ensure it can provide a robust and systematic nomenclature for these intriguing genes. All human RNA genes named to date can be found at the HGNC RNA webpage (http://www.genenames.org/rna).

Declarations

Acknowledgements

A number of researchers have provided invaluable support in naming various classes of RNAs: Sam Griffiths-Jones with miRNAs, Michel Weber with snoRNAs, Todd Lowe with tRNAs, Peter Stadler with U7 and vault RNAs, Shipra Agrawal with piRNAs and John Mattick with lncRNAs. Particular thanks go to former HGNC team member Kate Sneddon, and also to current colleagues Ruth Seal, Susan Gordon, Michael Lush and Louise Daugherty.

The work of HGNC is supported by National Human Genome Research Institute (NHGRI) grant P41 HG03345 and Wellcome Trust grant 081979/Z/07/Z.

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