English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

A missense mutation in the CSTF2 gene that impairs the function of the RNA recognition motif and causes defects in 3' end processing is associated with intellectual disability in humans

MPS-Authors
/persons/resource/persons50369

Kalscheuer,  Vera M.
Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)

Grozdanov_2020.pdf
(Publisher version), 7MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Grozdanov, P. N., Masoumzadeh, E., Kalscheuer, V. M., Bienvenu, T., Billuart, P., Delrue, M.-A., et al. (2020). A missense mutation in the CSTF2 gene that impairs the function of the RNA recognition motif and causes defects in 3' end processing is associated with intellectual disability in humans. Nucleic Acids Research (London), 48(17), 9804-9821. doi:10.1093/nar/gkaa689.


Cite as: http://hdl.handle.net/21.11116/0000-0007-B681-9
Abstract
CSTF2 encodes an RNA-binding protein that is essential for mRNA cleavage and polyadenylation (C/P). No disease-associated mutations have been described for this gene. Here, we report a mutation in the RNA recognition motif (RRM) of CSTF2 that changes an aspartic acid at position 50 to alanine (p.D50A), resulting in intellectual disability in male patients. In mice, this mutation was sufficient to alter polyadenylation sites in over 1300 genes critical for brain development. Using a reporter gene assay, we demonstrated that C/P efficiency of CSTF2D50A was lower than wild type. To account for this, we determined that p.D50A changed locations of amino acid side chains altering RNA binding sites in the RRM. The changes modified the electrostatic potential of the RRM leading to a greater affinity for RNA. These results highlight the significance of 3' end mRNA processing in expression of genes important for brain plasticity and neuronal development.