pubmed.ncbi.nlm.nih.gov

Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them - PubMed

Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them

M C Siomi et al. Mol Cell Biol. 1996 Jul.

Abstract

Fragile X syndrome, the most common form of hereditary mental retardation, usually results from lack of expression of the FMR1 gene. The FMR1 protein is a cytoplasmic RNA-binding protein. The RNA-binding activity of FMR1 is an essential feature of FMR1, as fragile X syndrome can also result from the expression of mutant FMR1 protein that is impaired in RNA binding. Recently, we described two novel cytoplasmic proteins, FXR1 and FXR2, which are both very similar in amino acid sequence to FMR1 and which also interact strongly with FMR1 and with each other. To understand the function of FMR1 and the FXR proteins, we carried out cell fractionation and sedimentation experiments with monoclonal antibodies to these proteins to characterize the complexes they form. Here, we report that the FMR1 and FXR proteins are associated with ribosomes, predominantly with 60S large ribosomal subunits. The FXR proteins are associated with 60S ribosomal subunits even in cells that lack FMR1 and that are derived from a fragile X syndrome patient, indicating that FMR1 is not required for this association. We delineated the regions of FMR1 that mediate its binding to 60S ribosomal subunits and the interactions among the FMR1-FXR family members. Both regions contain sequences predicted to have a high propensity to form coiled coil interactions, and the sequences are highly evolutionarily conserved in this protein family. The association of the FMR1, FXR1, and FXR2 proteins with ribosomes suggests they have functions in translation or mRNA stability.

PubMed Disclaimer

Cited by

Functional Mammalian Amyloids and Amyloid-Like Proteins.
Rubel MS, Fedotov SA, Grizel AV, Sopova JV, Malikova OA, Chernoff YO, Rubel AA. Rubel MS, et al. Life (Basel). 2020 Aug 21;10(9):156. doi: 10.3390/life10090156. Life (Basel). 2020. PMID: 32825636 Free PMC article. Review.
A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P.
Schenck A, Bardoni B, Moro A, Bagni C, Mandel JL. Schenck A, et al. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8844-9. doi: 10.1073/pnas.151231598. Epub 2001 Jul 3. Proc Natl Acad Sci U S A. 2001. PMID: 11438699 Free PMC article.
A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins.
Ishizuka A, Siomi MC, Siomi H. Ishizuka A, et al. Genes Dev. 2002 Oct 1;16(19):2497-508. doi: 10.1101/gad.1022002. Genes Dev. 2002. PMID: 12368261 Free PMC article.
The KH domains of Xenopus Vg1RBP mediate RNA binding and self-association.
Git A, Standart N. Git A, et al. RNA. 2002 Oct;8(10):1319-33. doi: 10.1017/s135583820202705x. RNA. 2002. PMID: 12403469 Free PMC article.
Antipsychotic Drug Responsiveness and Dopamine Receptor Signaling; Old Players and New Prospects.
Rampino A, Marakhovskaia A, Soares-Silva T, Torretta S, Veneziani F, Beaulieu JM. Rampino A, et al. Front Psychiatry. 2019 Jan 9;9:702. doi: 10.3389/fpsyt.2018.00702. eCollection 2018. Front Psychiatry. 2019. PMID: 30687136 Free PMC article. Review.

References

1. J Cell Biol. 1990 Sep;111(3):807-16 - PubMed
1. Cell. 1995 Aug 11;82(3):475-83 - PubMed
1. Cell. 1990 Dec 21;63(6):1205-18 - PubMed
1. EMBO J. 1991 Feb;10(2):459-66 - PubMed
1. Cell. 1991 May 31;65(5):905-14 - PubMed

Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them - PubMed