FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences
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 transcr...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/52621 |
| _version_ | 1828165829262311424 |
|---|---|
| author | Raeann Goering Laura I Hudish Bryan B Guzman Nisha Raj Gary J Bassell Holger A Russ Daniel Dominguez J Matthew Taliaferro |
| author_facet | Raeann Goering Laura I Hudish Bryan B Guzman Nisha Raj Gary J Bassell Holger A Russ Daniel Dominguez J Matthew Taliaferro |
| author_sort | Raeann Goering |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:51:28Z |
| format | Article |
| id | doaj.art-47f207fd2aa946859582473f69699e34 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:51:28Z |
| publishDate | 2020-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-47f207fd2aa946859582473f69699e342022-12-22T03:52:56ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.52621FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequencesRaeann Goering0https://orcid.org/0000-0002-0351-335XLaura I Hudish1Bryan B Guzman2https://orcid.org/0000-0002-2711-9533Nisha Raj3https://orcid.org/0000-0002-5980-5001Gary J Bassell4Holger A Russ5https://orcid.org/0000-0001-5117-2927Daniel Dominguez6J Matthew Taliaferro7https://orcid.org/0000-0001-7580-1433Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Boulder, United StatesBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Boulder, United StatesDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartments of Cell Biology and Neurology, Emory University School of Medicine, Atlanta, GeorgiaDepartments of Cell Biology and Neurology, Emory University School of Medicine, Atlanta, GeorgiaBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Boulder, United StatesDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Boulder, United States; RNA Bioscience Initiative, University of Colorado Anschutz Medical Campus, Boulder, United StatesThe 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.https://elifesciences.org/articles/52621RNA localizationFMRPfragile x syndrome |
| spellingShingle | Raeann Goering Laura I Hudish Bryan B Guzman Nisha Raj Gary J Bassell Holger A Russ Daniel Dominguez J Matthew Taliaferro FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences eLife RNA localization FMRP fragile x syndrome |
| title | FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences |
| title_full | FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences |
| title_fullStr | FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences |
| title_full_unstemmed | FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences |
| title_short | FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences |
| title_sort | fmrp promotes rna localization to neuronal projections through interactions between its rgg domain and g quadruplex rna sequences |
| topic | RNA localization FMRP fragile x syndrome |
| url | https://elifesciences.org/articles/52621 |
| work_keys_str_mv | AT raeanngoering fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences AT lauraihudish fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences AT bryanbguzman fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences AT nisharaj fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences AT garyjbassell fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences AT holgeraruss fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences AT danieldominguez fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences AT jmatthewtaliaferro fmrppromotesrnalocalizationtoneuronalprojectionsthroughinteractionsbetweenitsrggdomainandgquadruplexrnasequences |