@Article{Briese_Saal-Bauernschubert_Ji-hnRNP_and_its-PNAS2018,
  author =	 {Briese, Michael and Saal-Bauernschubert, Lena and Ji, 
                  Changhe and Moradi, Mehri and Ghanawi, Hanaa and Uhl, 
                  Michael and Appenzeller, Silke and Backofen, Rolf and 
                  Sendtner, Michael},
  title =	 {{hnRNP} {R} and its main interactor, the noncoding {RNA} 
                  {7SK}, coregulate the axonal transcriptome of motoneurons},
  journal =	 PNAS,
  year =	 {2018},
  volume =	 {115},
  number =	 {12},
  pages =	 {E2859-E2868},
  user =	 {backofen},
  pmid =	 {29507242},
  doi = 	 {10.1073/pnas.1721670115},
  issn = 	 {1091-6490},
  issn = 	 {0027-8424},
  abstract =	 {Disturbed RNA processing and subcellular transport 
                  contribute to the pathomechanisms of motoneuron diseases 
                  such as amyotrophic lateral sclerosis and spinal muscular 
                  atrophy. RNA-binding proteins are involved in these 
                  processes, but the mechanisms by which they regulate the 
                  subcellular diversity of transcriptomes, particularly in 
                  axons, are not understood. Heterogeneous nuclear 
                  ribonucleoprotein R (hnRNP R) interacts with several 
                  proteins involved in motoneuron diseases. It is located in 
                  axons of developing motoneurons, and its depletion causes 
                  defects in axon growth. Here, we used individual 
                  nucleotide-resolution cross-linking and immunoprecipitation 
                  (iCLIP) to determine the RNA interactome of hnRNP R in 
                  motoneurons. We identified approximately 3,500 RNA targets, 
                  predominantly with functions in synaptic transmission and 
                  axon guidance. Among the RNA targets identified by iCLIP, 
                  the noncoding RNA 7SK was the top interactor of hnRNP R. We 
                  detected 7SK in the nucleus and also in the cytosol of 
                  motoneurons. In axons, 7SK localized in close proximity to 
                  hnRNP R, and depletion of hnRNP R reduced axonal 7SK. 
                  Furthermore, suppression of 7SK led to defective axon growth 
                  that was accompanied by axonal transcriptome alterations 
                  similar to those caused by hnRNP R depletion. Using a series 
                  of 7SK-deletion mutants, we show that the function of 7SK in 
                  axon elongation depends on its interaction with hnRNP R but 
                  not with the PTEF-B complex involved in transcriptional 
                  regulation. These results propose a role for 7SK as an 
                  essential interactor of hnRNP R to regulate its function in 
                  axon maintenance.}
}