UMMS Affiliation

Program in Molecular Medicine

Publication Date

2019-08-21

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Neuroscience and Neurobiology | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

RNA-binding proteins (RBPs) function in higher-order assemblages such as RNA granules to regulate RNA localization and translation. The Fragile X homolog FXR2P is an RBP essential for formation of neuronal Fragile X granules that associate with axonal mRNA and ribosomes in the intact brain. However, the FXR2P domains important for assemblage formation in a cellular system are unknown. Here we used an EGFP insertional mutagenesis approach to probe for FXR2P intrinsic features that influence its structural states. We tested 18 different in-frame FXR2P(EGFP) fusions in neurons and found that the majority did not impact assemblage formation. However, EGFP insertion within a 23 amino acid region of the low complexity (LC) domain induced FXR2P(EGFP) assembly into two distinct fibril states that were observed in isolation or in highly-ordered bundles. FXR2P(EGFP) fibrils exhibited different developmental timelines, ultrastructures and ribosome associations. Formation of both fibril types was dependent on an intact RNA-binding domain. These results suggest that restricted regions of the LC domain, together with the RNA-binding domain, may be important for FXR2P structural state organization in neurons.

Keywords

Fragile X syndrome, Local protein synthesis, Low complexity, RNA granule, RNA-binding protein

Rights and Permissions

© 2019. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

DOI of Published Version

10.1242/bio.046383

Source

Biol Open. 2019 Aug 21;8(8). pii: 8/8/bio046383. doi: 10.1242/bio.046383. Link to article on publisher's site

Journal/Book/Conference Title

Biology open

Related Resources

Link to Article in PubMed

PubMed ID

31434643

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.