An integrated DNA and RNA variant detector identifies a highly conserved three base exon in the MAP4K5 kinase locus
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F21%3A00078661" target="_blank" >RIV/00209805:_____/21:00078661 - isvavai.cz</a>
Result on the web
<a href="https://pubmed.ncbi.nlm.nih.gov/34190025/" target="_blank" >https://pubmed.ncbi.nlm.nih.gov/34190025/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/15476286.2021.1932345" target="_blank" >10.1080/15476286.2021.1932345</a>
Alternative languages
Result language
angličtina
Original language name
An integrated DNA and RNA variant detector identifies a highly conserved three base exon in the MAP4K5 kinase locus
Original language description
RNA variants that emerge from editing and alternative splicing form important regulatory stages in protein signalling. In this report, we apply an integrated DNA and RNA variant detection workbench to define the range of RNA variants that deviate from the reference genome in a human melanoma cell model. The RNA variants can be grouped into (i) classic ADAR-like or APOBEC-like RNA editing events and (ii) multiple-nucleotide variants (MNVs) including three and six base pair in-frame non-canonical unmapped exons. We focus on validating representative genes of these classes. First, clustered nonsynonymous RNA edits (A-I) in the CDK13 gene were validated by Sanger sequencing to confirm the integrity of the RNA variant detection workbench. Second, a highly conserved RNA variant in the MAP4K5 gene was detected that results most likely from the splicing of a non-canonical three-base exon. The two RNA variants produced from the MAP4K5 locus deviate from the genomic reference sequence and produce V569E or V569del isoform variants. Low doses of splicing inhibitors demonstrated that the MAP4K5-V569E variant emerges from an SF3B1-dependent splicing event. Mass spectrometry of the recombinant SBP-tagged MAP4K5V569E and MAP4K5V569del proteins pull-downs in transfected cell systems was used to identify the protein-protein interactions of these two MAP4K5 isoforms and propose possible functions. Together these data highlight the utility of this integrated DNA and RNA variant detection platform to detect RNA variants in cancer cells and support future analysis of RNA variant detection in cancer tissue.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molecular, cellular and clinical approach to healthy ageing</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
RNA Biology
ISSN
1547-6286
e-ISSN
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Volume of the periodical
18
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
2556-2575
UT code for WoS article
000668485500001
EID of the result in the Scopus database
2-s2.0-85109157041