Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F13%3A00070459" target="_blank" >RIV/00216224:14740/13:00070459 - isvavai.cz</a>
Result on the web
<a href="http://www.nature.com/nsmb/journal/v20/n12/pdf/nsmb.2698.pdf" target="_blank" >http://www.nature.com/nsmb/journal/v20/n12/pdf/nsmb.2698.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/nsmb.2698" target="_blank" >10.1038/nsmb.2698</a>
Alternative languages
Result language
angličtina
Original language name
Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43
Original language description
TDP-43 encodes an alternative-splicing regulator with tandem RNA-recognition motifs (RRMs). The protein regulates cystic fibrosis transmembrane regulator ( CFTR ) exon 9 splicing through binding to long UG-rich RNA sequences and is found in cytoplasmic inclusions of several neurodegenerative diseases. We solved the solution structure of the TDP-43 RRMs in complex with UG-rich RNA. Ten nucleotides are bound by both RRMs, and six are recognized sequence specifically. Among these, a central G interacts with both RRMs and stabilizes a new tandem RRM arrangement. Mutations that eliminate recognition of this key nucleotide or crucial inter-RRM interactions disrupt RNA binding and TDP-43?dependent splicing regulation. In contrast, point mutations that affectbase-specific recognition in either RRM have weaker effects. Our findings reveal not only how TDP-43 recognizes UG repeats but also how RNA binding?dependent inter-RRM interactions are crucial for TDP-43 function.
Czech name
—
Czech description
—
Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
—
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
2013
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
NATURE STRUCTURAL & MOLECULAR BIOLOGY
ISSN
1545-9993
e-ISSN
—
Volume of the periodical
20
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
1443-1449
UT code for WoS article
000328007600017
EID of the result in the Scopus database
—