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Nuclear factor TDP‐43 can affect selected microRNA levels
Author(s) -
Buratti Emanuele,
De Conti Laura,
Stuani Cristiana,
Romano Maurizio,
Baralle Marco,
Baralle Francisco
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07643.x
Subject(s) - drosha , microrna , gene knockdown , frontotemporal lobar degeneration , biology , rna splicing , amyotrophic lateral sclerosis , tardbp , genetics , transcription factor , frontotemporal dementia , microbiology and biotechnology , rna interference , gene , rna , medicine , pathology , mutant , dementia , disease , sod1
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.