Journal Article

FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences

Taliaferro, J Matthew, Hudish, Laura I, Guzman, Bryan B, Russ, Holger A, Raj, Nisha, Goering, Raeann, Bassell, Gary J, Dominguez, Daniel

2020

Overview

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.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Animals / Axons / Cell cycle / Cells, Cultured / Chromosomes and Gene Expression / Experiments / FMRP / Fragile X Mental Retardation Protein - chemistry / Fragile X Mental Retardation Protein - genetics / Fragile X Mental Retardation Protein - metabolism / Fragile X Syndrome / G-Quadruplexes / Gene expression / Gene Knockout Techniques / Genetics and Genomics / Intellectual disabilities / Localization / Membranes / Mice / Neurites - metabolism / Neurons - metabolism / Proteins / Ribonucleic acid / Ribosomes / RNA / RNA localization / RNA Transport - genetics / RNA, Messenger - chemistry / RNA, Messenger - genetics / RNA, Messenger - metabolism / RNA-binding protein