WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies
Authors: Irene Weibrecht
Stephen Smith
Salah Mahmoudi
Klas G Wiman
Ola Söderberg
Sofia Henriksson
Marianne Farnebo
Staffan Strömblad
Journal: PLoS Biology (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: WRAP53 gene; p53 antisense transcript; Cajal bodies; ribonucleoproteins; splicing
Affiliations: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, 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 importinβ, and that WRAP53 is essential for complex formation between SMN-coilin and SMN-importinβ. 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 important for nuclear targeting of SMN and the subsequent localization of the SMN complex to Cajal bodies. Moreover, we detect reduced WRAP53-SMN binding in patients with spinal muscular atrophy, which is the leading genetic cause of infant mortality worldwide, caused by mutations in SMN1. This suggests that loss of WRAP53-mediated SMN trafficking contributes to spinal muscular atrophy. 

Retracted: No

PubPeer comments:
 September 2018 correction:  * Fig 3 is incorrect. The authors have provided a corrected version here. The left panel of Fig 3A has been replaced with a replicate. This panel was accidentally swapped and the data for IB: WRAP53 was reused in Fig 6C. The legend remains the same. * Fig 5 is incorrect. The authors have provided a corrected version here. A splice-line has been included to clearly indicate the lanes in Fig 5D. The legend remains the same. * Fig 7 is incorrect. The authors have provided a corrected version here. The lower left image (IB: coilin) of Fig 7C has been flipped as it was originally presented upside down. A new legend is provided. , 
 September 2018 correction: https: journals.plos.org plosbiology article?id=10.1371 journal.pbio.3000030 It reads:  *Fig 3 is incorrect. The authors have provided a corrected version here. The left panel of Fig 3A has been replaced with a replicate. This panel was accidentally swapped and the data for IB: WRAP53 was reused in Fig 6C. The legend remains the same.* Here is the original Figure 3A with a duplicated panel compared to Figure 6C, marked with red boxes as reported to the journal in October 2015. ![file] ,