tailieunhanh - Báo cáo khoa học: Nuclear factor TDP-43 can affect selected microRNA levels

TDP-43 has recently been described as the major component of the inclu-sions found in the brain of patients with a variety of neurodegenerative dis-eases, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 is a ubiquitous protein whose specific functions are prob-ably crucial to establishing its pathogenic role. | Nuclear factor TDP-43 can affect selected microRNA levels Emanuele Buratti1 Laura De Conti1 Cristiana Stuani1 Maurizio Romano2 Marco Baralle1 and Francisco Baralle1 1 InternationalCentre for Genetic Engineering and Biotechnology ICGEB Trieste Italy 2 Department of Life Sciences University of Trieste Italy Keywords amyotrophic lateral sclerosis let-7b microRNAs miR-663 TDP-43 Correspondence F. E. Baralle Padriciano 99 34012 Trieste Italy Fax 39 040 3757361 Tel 39 040 3757337 E-mail baralle@ Received 2 September 2009 revised 26 February 2010 accepted 8 March 2010 doi 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. Introduction TDP-43 is a protein belonging to the hnRNP class of nuclear factors that has been described to play a role in a variety of cellular processes including gene transcription .