Journal
ELIFE
Volume 9, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.52621
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Funding
- Boettcher Foundation [AWD182937]
- National Institutes of Health [NIH1R35GM133885, NIHDK120444, NIHAI140044, NIHDK118803-01A1, NIH1R01MH109026, 1U54HD082013, NIH-T32-GM008730]
- Guild ACORN
- Colorado Clinical and Translational Sciences Institute
- Children's Diabetes Foundation
- NIH NIH/HIRN consortium new investigator award
- Culshaw Junior Investigator Award
- Juvenile Diabetes Research Foundation
- Human Islet Research Network NIH/HIRN consortium new investigator award
- University of Colorado RNA Bioscience Initiative
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The sorting of RNA molecules to subcellular locations facilitates the activity of spatially restricted processes. We have analyzed subcellular transcriptomes of FMRP-null mouse neuronal cells to identify transcripts that depend on FMRP for efficient transport to neurites. We found that these transcripts contain an enrichment of G-quadruplex sequences in their 3' UTRs, suggesting that FMRP recognizes them to promote RNA localization. We observed similar results in neurons derived from Fragile X Syndrome patients. We identified the RGG domain of FMRP as important for binding G-quadruplexes and the transport of G-quadruplex-containing transcripts. Finally, we found that the translation and localization targets of FMRP were distinct and that an FMRP mutant that is unable to bind ribosomes still promoted localization of G-quadruplex-containing messages. This suggests that these two regulatory modes of FMRP may be functionally separated. These results provide a framework for the elucidation of similar mechanisms governed by other RNA-binding proteins.
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