Nuclear factor TDP-43 can affect selected microRNA levels

FEBS J. 2010 May;277(10):2268-81. doi: 10.1111/j.1742-4658.2010.07643.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence / genetics
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / genetics
  • Epoxide Hydrolases / genetics
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics*
  • Genes, Reporter / genetics
  • HeLa Cells
  • Humans
  • Laminin / genetics
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Binding / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Tyrosine Kinases / genetics
  • Qa-SNARE Proteins / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Ribonuclease III / metabolism
  • Up-Regulation / genetics
  • Vesicle-Associated Membrane Protein 3 / genetics

Substances

  • DNA-Binding Proteins
  • Laminin
  • MicroRNAs
  • Qa-SNARE Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Proteins
  • VAMP3 protein, human
  • Vesicle-Associated Membrane Protein 3
  • laminin gamma 1
  • mirnlet7 microRNA, human
  • Luciferases
  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • DROSHA protein, human
  • Ribonuclease III
  • Epoxide Hydrolases
  • EPHX1 protein, human