Systematics for types and effects of RNA variations

Abstract

Systematics is described for annotation of variations in RNA molecules. The conceptual framework is part of Variation Ontology (VariO) and facilitates depiction of types of variations, their functional and structural effects and other consequences in any RNA molecule in any organism. There are more than 150 RNA related VariO terms in seven levels, which can be further combined to generate even more complicated and detailed annotations. The terms are described together with examples, usually for variations and effects in human and in diseases. RNA variation type has two subcategories: variation classification and origin with subterms. Altogether six terms are available for function description. Several terms are available for affected RNA properties. The ontology contains also terms for structural description for affected RNA type, post-transcriptional RNA modifications, secondary and tertiary structure effects and RNA sugar variations. Together with the DNA and protein concepts and annotations, RNA terms allow comprehensive description of variations of genetic and non-genetic origin at all possible levels. The VariO annotations are readable both for humans and computer programs for advanced data integration and mining.

When a Synonymous Variant Is Nonsynonymous

“…Putative synonymous variants can have various effects on RNA level [ 4 ] ( Figure 2 ). Most frequently such variants with an effect impair splicing, either by altering splicing site [ 9 ] or splicing regulatory motif, such as exonic splicing enhancer (ESE) [ 10 ] or exonic splicing silencer (ESS) [ 11 ].…”

“…Description of RNA variations can be complicated as there are numerous types [ 4 ], see Figure 1 . Starting with the genetics textbooks, single nucleotide variants (SNVs) in mRNA coding region are wrongly classified only to three classes: missense, nonsense and synonymous (also called silent).…”

Individual Genetic Heterogeneity

“…The ontology has been updated and it organizes systematically the concepts described in this text. VariO-based detailed descriptions of variation types have been presented previously for DNA (Vihinen, 2018), RNA (Vihinen, 2021b) and protein variants (Vihinen, 2015b) along with examples, often in relation to human diseases.…”

“…Variations in RNA (Figures 1L and 1M) comprise RNA deletions, insertions, indels, substitutions, translocations including inversions, as well as missing RNA, and changes in initiation and termination codon (Vihinen, 2021b). In the coding regions, insertions, indels and deletions are either in-frame or out-of-frame, indicating whether the amino acid code is retained or not.…”

“…Post translational modification sites in blue, the majority of the sites are not shown as the flexible termini are not included to the structure. Adapted from (Vihinen, 2015b(Vihinen, , 2018(Vihinen, , 2021b. Sex determination of offspring C) in XX/XY system.…”