High-throughput analysis revealed mutations’ diverging effects on SMN1 exon 7 splicing
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F19%3AN0000022" target="_blank" >RIV/00209775:_____/19:N0000022 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/19:00107593
Result on the web
<a href="https://www.tandfonline.com/doi/full/10.1080/15476286.2019.1630796?scroll=top&needAccess=true" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/15476286.2019.1630796?scroll=top&needAccess=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/15476286.2019.1630796" target="_blank" >10.1080/15476286.2019.1630796</a>
Alternative languages
Result language
angličtina
Original language name
High-throughput analysis revealed mutations’ diverging effects on SMN1 exon 7 splicing
Original language description
Splicing-affecting mutations can disrupt gene function by altering the transcript assembly. To ascertain splicing dysregulation principles, we modified a minigene assay for the parallel high-throughput evaluation of different mutations by next-generation sequencing. In our model system, all exonic and six intronic positions of the SMN1 gene’s exon 7 were mutated to all possible nucleotide variants, which amounted to 180 unique single-nucleotide mutants and 470 double mutants. The mutations resulted in a wide range of splicing aberrations. Exonic splicing-affecting mutations resulted either in substantial exon skipping, supposedly driven by predicted exonic splicing silencer or cryptic donor splice site (5′ss) and de novo 5′ss strengthening and use. On the other hand, a single disruption of exonic splicing enhancer was not sufficient to cause major exon skipping, suggesting these elements can be substituted during exon recognition. While disrupting the acceptor splice site led only to exon skipping, some 5′ss mutations potentiated the use of three different cryptic 5′ss. Generally, single mutations supporting cryptic 5′ss use displayed better pre-mRNA/U1 snRNA duplex stability and increased splicing regulatory element strength across the original 5′ss. Analyzing double mutants supported the predominating splicing regulatory elements’ effect, but U1 snRNA binding could contribute to the global balance of splicing isoforms. Based on these findings, we suggest that creating a new splicing enhancer across the mutated 5′ss can be one of the main factors driving cryptic 5′ss use.
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
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
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
16
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
1364-1376
UT code for WoS article
000472379600001
EID of the result in the Scopus database
2-s2.0-85067683899