wrap53 is essential for cajal body formation and for targeting the survival of motor neuron complex to cajal bodieswrap53对卡哈尔的身体是至关重要的形成和运动神经元的生存目标复杂卡哈尔尸体.pdf

WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies 1 1 2 3 ¨ 2 Salah Mahmoudi , Sofia Henriksson , Irene Weibrecht , Stephen Smith , Ola Soderberg , Staffan ¨ 3 1 1 Stromblad , Klas G. Wiman , Marianne Farnebo * 1 Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden, 2 Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden, 3 Center for Biosciences, Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden Abstract The WRAP53 gene gives rise to a p53 antisense transcript that regulates p53. This gene also encodes a protein that directs small Cajal body–specific RNAs to Cajal bodies. Cajal bodies are nuclear organelles involved in diverse functions such as processing ribonucleoproteins important for splicing. Here we identify the WRAP53 protein as an essential factor for Cajal body maintenance and for directing the survival of motor neuron (SMN) complex to Cajal bodies. By RNA interference and immunofluorescence we show that Cajal bodies collapse without WRAP53 and that new Cajal bodies cannot be formed. By immunoprecipitation we find that WRAP53 associates with the Cajal body marker coilin, the splicing regulatory protein SMN, and the nuclear import receptor importinb, and that WRAP53 is essential for complex formation between SMN–coilin and SMN–importinb. Furthermore, depletion of WRAP53 leads to accumulation of SMN in the cytoplasm and prevents the SMN complex from reaching Cajal bodies. Thus, WRAP53 mediates the interaction between SMN and associated proteins, which is impo