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Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
EGFP insertional mutagenesis reveals multiple FXR2P fibrillar states with differing ribosome association in neurons
Biology open, v 8(8)
15 Aug 2019
PMID: 31434643
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
Summary:
A mutagenesis study reveals that the higher-order structural states of the RBP FXR2P in neurons can be regulated by manipulation of the LC and RNA-binding domains.
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Details
- Title
- EGFP insertional mutagenesis reveals multiple FXR2P fibrillar states with differing ribosome association in neurons
- Creators
- Emily E. Stackpole - Brown UniversityMichael R. Akins - Drexel UniversityMaria Ivshina - , , , , , , , , , , , , , , ,Anastasia C. Murthy - Brown UniversityNicolas L. Fawzi - Brown UniversityJustin R. Fallon - Brown University
- Publication Details
- Biology open, v 8(8)
- Publisher
- The Company of Biologists Ltd
- Grant note
- HD052083 / ; R01GM118530 / ; T32NS062443 / ; MH090237 / ;
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000484809100022
- Scopus ID
- 2-s2.0-85071875913
- Other Identifier
- 991019168340404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biology