@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},
doi = {10.1073/pnas.1721670115},
volume = {115},
user = {backofen},
pmid = {29507242},
pages = {E2859-E2868},
number = {12},
issn = {1091-6490},
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.}
}