scholarly journals Expression, localization and tau exon 10 splicing activity of the brain RNA-binding protein TNRC4

2007 ◽  
Vol 16 (22) ◽  
pp. 2760-2769 ◽  
Author(s):  
J. P. Chapple ◽  
K. Anthony ◽  
T. R. Martin ◽  
A. Dev ◽  
T. A. Cooper ◽  
...  
2018 ◽  
Author(s):  
Michael A. Rieger ◽  
Dana M. King ◽  
Barak A. Cohen ◽  
Joseph D. Dougherty

AbstractCELF6 is a RNA-binding protein in a family of proteins with roles in human health and disease, however little is known about the mRNA targets or in vivo function of this protein. We utilized CLIP-Seq to identify, for the first time, in vivo targets of CELF6 and identify hundreds of transcripts bound by CELF6 in the brain. We found these are disproportionately mRNAs coding for synaptic proteins. We then conducted functional validation of these targets, testing greater than 400 CELF6 bound sequence elements for their activity, applying a massively parallel reporter assay framework to evaluation of the CLIP data. We also mutated potential binding motifs within these elements and tested their impact. This comprehensive analysis led us to ascribe a previously unknown function to CELF6: we found bound elements were generally repressive of translation, that CELF6 further enhances this repression via decreasing RNA abundance, and this process was dependent on UGU-rich sequence motifs. This greatly extends the known role for CELF6, which had previously been defined only as a splicing factor. We further extend these findings by demonstrating the same function for CELF3, CELF4, and CELF5. Finally, we demonstrate that the CELF6 targets are derepressed in CELF6 mutant mice in vivo, confirming this new role in the brain. Thus, our study demonstrates that CELF6 and other sub-family members are repressive CNS RNA-binding proteins, and CELF6 downregulates specific mRNAs in vivo.


2004 ◽  
Vol 279 (30) ◽  
pp. 31440-31444 ◽  
Author(s):  
Paolo Macchi ◽  
Amy M. Brownawell ◽  
Barbara Grunewald ◽  
Luc DesGroseillers ◽  
Ian G. Macara ◽  
...  

PLoS Genetics ◽  
2013 ◽  
Vol 9 (4) ◽  
pp. e1003474 ◽  
Author(s):  
Ingrid Ehrmann ◽  
Caroline Dalgliesh ◽  
Yilei Liu ◽  
Marina Danilenko ◽  
Moira Crosier ◽  
...  

2006 ◽  
Vol 172 (2) ◽  
pp. 221-231 ◽  
Author(s):  
Bernhard Goetze ◽  
Fabian Tuebing ◽  
Yunli Xie ◽  
Mario M. Dorostkar ◽  
Sabine Thomas ◽  
...  

Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression is largely restricted to the brain. It is thought to play a role in the delivery of RNA to dendrites of polarized neurons. To investigate the function of Stau2 in mature neurons, we interfered with Stau2 expression by RNA interference (RNAi). Mature neurons lacking Stau2 displayed a significant reduction in the number of dendritic spines and an increase in filopodia-like structures. The number of PSD95-positive synapses and miniature excitatory postsynaptic currents were markedly reduced in Stau2 down-regulated neurons. Akin effects were caused by overexpression of dominant-negative Stau2. The observed phenotype could be rescued by overexpression of two RNAi cleavage-resistant Stau2 isoforms. In situ hybridization revealed reduced expression levels of β-actin mRNA and fewer dendritic β-actin mRNPs in Stau2 down-regulated neurons. Thus, our data suggest an important role for Stau2 in the formation and maintenance of dendritic spines of hippocampal neurons.


2007 ◽  
Vol 177 (4S) ◽  
pp. 78-79
Author(s):  
Lioudmila Sitnikova ◽  
Gary Mendese ◽  
Qin Lui ◽  
Bruce A. Woda ◽  
Di Lu ◽  
...  

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