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

ELife
Raeann GoeringJ. Matthew Taliaferro

Abstract

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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Citations

Sep 23, 2020·Open Biology·Benita Turner-BridgerJean-Michel Cioni
Oct 16, 2020·Traffic·Brooke R D'Arcy, Debra L Silver
Dec 12, 2020·Trends in Biochemical Sciences·Leïla DumasStefania Millevoi
Mar 28, 2021·Nucleic Acids Research·Kaixin LyuChun Kit Kwok
Apr 28, 2021·The FEBS Journal·John W Cave, Dianna E Willis
Jun 5, 2021·Nature Communications·Gabrijela DumbovićJohn L Rinn
Jun 5, 2021·Nucleic Acids Research·Alexandros ArmaosGian Gaetano Tartaglia
Jun 1, 2021·Seminars in Cell & Developmental Biology·Jocelyn WidagdoVictor Anggono
Jul 13, 2021·Bio-protocol·Ankita AroraMatthew J Taliaferro
Feb 8, 2022·ELife·Young J Yoon, Gary J Bassell

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Datasets Mentioned

BETA
BC079671.1

Methods Mentioned

BETA
scraping
CLIP-seq
CLIP
dot blot
RBNS
smFISH
PCR
RNAseq
size exclusion chromatography
in vitro transcription

Software Mentioned

FISH
DESeq2
R package Xtail
kallisto
txImport
PhyloP
Xtail
seqBias
salmon
quant

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