6Q2I

Solution state NMR structures of the RNA recognition motif (RRM) domain of human CstF-64

Summary for 6Q2I

• Entry DOI: 10.2210/pdb6q2i/pdb
• Related: 1p1t
• NMR Information: BMRB: 30652
• Descriptor: Cleavage stimulation factor subunit 2 (1 entity in total)
• Functional Keywords: rna recognition motif, rna cleavage and polyadenylation, rna binding protein, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 12095.45

Authors

Latham, M.P.,Masoumzadeh, E. (deposition date: 2019-08-08, release date: 2020-08-12, Last modification date: 2024-05-01)

Primary citation

Grozdanov, P.N.,Masoumzadeh, E.,Kalscheuer, V.M.,Bienvenu, T.,Billuart, P.,Delrue, M.A.,Latham, M.P.,MacDonald, C.C.
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 Res., 48:9804-9821, 2020

PubMed 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.

PubMed: 32816001
DOI: 10.1093/nar/gkaa689

Experimental method

SOLUTION NMR