2001/09/01 by Emanuele Buratti, Francisco E. Baralle · 1 citation
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer
paper · pdf · doi:10.1074/jbc.m104236200
openalex publication_date 2001/09/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/05
Variations in a polymorphic (TG)m sequence near exon 9 of the human CFTR gene have been associated with variable proportions of exon skipping and occurrence of disease. We have recently identified nuclear factor TDP-43 as a novel splicing regulator capable of binding to this element in the CFTR pre-mRNA and inhibiting recognition of the neighboring exon. In this study we report the dissection of the RNA binding properties of TDP-43 and their functional implications in relationship with the splicing process. Our results show that this protein contains two fully functional RNA recognition motif (RRM) domains with distinct RNA/DNA binding characteristics. Interestingly, TDP-43 can bind a minimum number of six UG (or TG) single-stranded dinucleotide stretches, and binding affinity increases with the number of repeats. In particular, the highly conserved Phe residues in the first RRM region play a key role in nucleic acid recognition.