Cancer-Associated Substitutions in RNA Recognition Motifs of PUF60 and U2AF65 Reveal Residues Required for Correct Folding and 3 ' Splice-Site Selection

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00118245" target="_blank" >RIV/00216224:14740/20:00118245 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/2072-6694/12/7/1865" target="_blank" >https://www.mdpi.com/2072-6694/12/7/1865</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers12071865" target="_blank" >10.3390/cancers12071865</a>

Result language

angličtina

Original language name

Cancer-Associated Substitutions in RNA Recognition Motifs of PUF60 and U2AF65 Reveal Residues Required for Correct Folding and 3 ' Splice-Site Selection

Original language description

U2AF65 (U2AF2) and PUF60 (PUF60) are splicing factors important for recruitment of the U2 small nuclear ribonucleoprotein to lariat branch points and selection of 3 ' splice sites (3 ' ss). Both proteins preferentially bind uridine-rich sequences upstream of 3 ' ss via their RNA recognition motifs (RRMs). Here, we examined 36 RRM substitutions reported in cancer patients to identify variants that alter 3 ' ss selection, RNA binding and protein properties. Employing PUF60- and U2AF65-dependent 3 ' ss previously identified by RNA-seq of depleted cells, we found that 43% (10/23) and 15% (2/13) of independent RRM mutations in U2AF65 and PUF60, respectively, conferred splicing defects. At least three RRM mutations increased skipping of internalU2AF2(similar to 9%, 2/23) orPUF60(similar to 8%, 1/13) exons, indicating that cancer-associated RRM mutations can have bothcis- andtrans-acting effects on splicing. We also report residues required for correct folding/stability of each protein and map functional RRM substitutions on to existing high-resolution structures of U2AF65 and PUF60. These results identify new RRM residues critical for 3 ' ss selection and provide relatively simple tools to detect clonal RRM mutations that enhance the mRNA isoform diversity.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers

ISSN

2072-6694

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

7

Country of publishing house

CH - SWITZERLAND

Number of pages

19

Pages from-to

1865

UT code for WoS article

000556370000001

EID of the result in the Scopus database

2-s2.0-85087799579