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TDP-43 Binds Heterogeneous Nuclear Ribonucleoprotein A/B through Its C-terminal Tail

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Buratti, Emanuele, Brindisi, Antonia, Giombi, Maurizio, Tisminetzky, Sergio, Ayala, Youhna M., Baralle, Francisco E.·2005·Journal of Biological Chemistry

Abstract

TDP-43 is a highly conserved nuclear factor of yet unknown function that binds to ug-repeated sequences and is responsible for cystic fibrosis transmembrane conductance regulator exon 9 splicing inhibition. We have analyzed TDP-43 interactions with other splicing factors and identified the critical regions for the protein/protein recognition events that determine this biological function. We show here that the C-terminal region of TDP-43 is capable of binding directly to several proteins of the heterogeneous nuclear ribonucleoprotein (hnRNP) family with well known splicing inhibitory activity, in particular, hnRNP A2/B1 and hnRNP A1. Mutational analysis showed that TDP-43 proteins lacking the C-terminal region could not inhibit splicing probably because they were unable to form the hnRNP-rich complex involved in splicing inhibition. Finally, through splicing complex analysis, we show that splicing inhibition mediated by TDP-43 occurs at the earliest stages of spliceosomal assembly.

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Metadata

Authors
Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S., Ayala, Y. M., & Baralle, F. E.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2005-11
Volume
280
Issue
45
Pages
37572-37584
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2060076138
Cited by
460
References
4
FWCI
3.80
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: TDP-43 Binds Heterogeneous Nuclear Ribonucleoprotein A/B through Its C-terminal Tail. https://app.cochat.ai/papers/10.1074/jbc.m505557200
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Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S., Ayala, Y. M., & Baralle, F. E. (2005). TDP-43 Binds Heterogeneous Nuclear Ribonucleoprotein A/B through Its C-terminal Tail. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m505557200

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