title: Nuclear factor TDP-43 can affect selected microRNA levels.
abstract: TDP-43 has recently been described as the major component of the inclusions found in the brain of patients with a variety of neurodegenerative diseases, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 is a ubiquitous protein whose specific functions are probably crucial to establishing its pathogenic role. Apart from its involvement in transcription, splicing and mRNA stability, TDP-43 has also been described as a Drosha-associated protein. However, our knowledge of the role of TDP-43 in the microRNA (miRNA) synthesis pathway is limited to the association mentioned above. Here we report for the first time which changes occur in the total miRNA population following TDP-43 knockdown in culture cells. In particular, we have observed that let-7b and miR-663 expression levels are down- and upregulated, respectively. Interestingly, both miRNAs are capable of binding directly to TDP-43 in different positions: within the miRNA sequence itself (let-7b) or in the hairpin precursor (miR-663). Using microarray data and real-time PCR we have also identified several candidate transcripts whose expression levels are selectively affected by these TDP-43-miRNA interactions.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Buratti
authors.forename: Laura
authors.initials: L
authors.lastname: De Conti
authors.forename: Cristiana
authors.initials: C
authors.lastname: Stuani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Romano
authors.forename: Marco
authors.initials: M
authors.lastname: Baralle
authors.forename: Francisco
authors.initials: F
authors.lastname: Baralle
mesh_terms: D001483:Base Sequence / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007797:Laminin / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D050765:Qa-SNARE Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D051040:Vesicle-Associated Membrane Protein 3 / Q000235:genetics; D000097603:Dyrk Kinases
chemical_list: D004268:DNA-Binding Proteins; D004851:Epoxide Hydrolases; D007797:Laminin; D008156:Luciferases; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D050765:Qa-SNARE Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D043244:Ribonuclease III; D051040:Vesicle-Associated Membrane Protein 3; D000097603:Dyrk Kinases; C494946:VAMP3 protein, human; C089141:laminin gamma 1; C487931:mirnlet7 microRNA, human; C517918:DROSHA protein, human; C522330:EPHX1 protein, human