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Review
. 2020 Dec;39(4):1039-1049.
doi: 10.1007/s10555-020-09920-8. Epub 2020 Aug 8.

Splice variants of RAS-translational significance

Erzsébet Rásó  1
Affiliations
Review

Splice variants of RAS-translational significance

Erzsébet Rásó. Cancer Metastasis Rev. 2020 Dec.

Abstract

One of the mechanisms potentially explaining the discrepancy between the number of human genes and the functional complexity of organisms is generating alternative splice variants, an attribute of the vast majority of multi-exon genes. Members of the RAS family, such as NRAS, KRAS and HRAS, all of which are of significant importance in cancer biology, are no exception. The structural and functional differences of these splice variants, particularly if they contain the canonical (and therefore routinely targeted for diagnostic purposes) hot spot mutations, pose a significant challenge for targeted therapies. We must therefore consider whether these alternative splice variants constitute a minor component as originally thought and how therapies targeting the canonical isoforms affect these alternative splice variants and their overall functions.

Keywords: Expression; Function; HRAS; KRAS; NRAS; Splicing.

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Figures

Fig. 1
Fig. 1
Comparison of the coding nucleotide sequences of exon 2 of the three RAS molecules reveals that even though 57% of the codons are coded by different triplets, protein level homology is 100%
Fig. 2
Fig. 2
Alternative splice variants of NRAS [58]. These are the isoforms described in the literature. Ensembl only records isoform 1
Fig. 3
Fig. 3
Alternative splice variants of HRAS [64]. Even today, HRAS204 is mostly referred to as p19H-RasIDX
Fig. 4
Fig. 4
Alterative splice variants of KRAS in human (KRAS) and mouse (Kras) hosts according to the Ensembl database. Phylogenetic conservatism is evident. Interestingly, even though the introns are dramatically different between the two species, the splice sites are clearly marking identical exons
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