Essential role for KH domains in RNA binding

Impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome

Haruhiko Siomi, Mleyoung Choi, Mikiko C. Siomi, Robert L. Nussbaum, Gideon Dreyfuss

Research output: Contribution to journalArticle

349 Citations (Scopus)

Abstract

The KH domain is an evolutionarily conserved sequence motif present in many RNA-binding proteins, including the pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). We assessed the role of KH domains in RNA binding by mutagenesis of KH domains in hnRNP K and FMR1. Conserved residues of all three hnRNP K KH domains are required for its wild-type RNA binding. Interestingly, while fragile X syndrome is usually caused by lack of FMR1 expression, a previously reported mutation in a highly conserved residue of one of its two KH domains (IIe-304→Asn) also results in mental retardation. We found that the binding of this mutant protein to RNA is severely impaired. These results demonstrate an essential role for KH domains in RNA binding. Furthermore, they strengthen the connection between fragile X syndrome and loss of the RNA binding activity of FMR1.

Original languageEnglish
Pages (from-to)33-39
Number of pages7
JournalCell
Volume77
Issue number1
DOIs
Publication statusPublished - 1994 Apr 8
Externally publishedYes

Fingerprint

Heterogeneous-Nuclear Ribonucleoprotein K
Fragile X Syndrome
RNA
Intellectual Disability
Mutation
RNA-Binding Proteins
Conserved Sequence
RNA Precursors
Mutant Proteins
Mutagenesis
Carrier Proteins
Genes
RNA-Binding Motifs

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Essential role for KH domains in RNA binding : Impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome. / Siomi, Haruhiko; Choi, Mleyoung; Siomi, Mikiko C.; Nussbaum, Robert L.; Dreyfuss, Gideon.

In: Cell, Vol. 77, No. 1, 08.04.1994, p. 33-39.

Research output: Contribution to journalArticle

Siomi, Haruhiko ; Choi, Mleyoung ; Siomi, Mikiko C. ; Nussbaum, Robert L. ; Dreyfuss, Gideon. / Essential role for KH domains in RNA binding : Impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome. In: Cell. 1994 ; Vol. 77, No. 1. pp. 33-39.
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