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Preferential binding of a stable G3 BP ribonucleoprotein complex to intron‐retaining transcripts in mouse brain and modulation of their expression in the cerebellum
Author(s) -
Martin Sophie,
Bellora Nicolas,
GonzálezVallinas Juan,
Irimia Manuel,
Chebli Karim,
Toledo Marion,
Raabe Monika,
Eyras Eduardo,
Urlaub Henning,
Blencowe Ben J.,
Tazi Jamal
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13768
Subject(s) - biology , intron , rna splicing , rna binding protein , microbiology and biotechnology , ribonucleoprotein , rna , stress granule , messenger rna , gene , genetics , translation (biology)
Neuronal granules play an important role in the localization and transport of translationally silenced messenger ribonucleoproteins in neurons. Among the factors associated with these granules, the RNA ‐binding protein G3 BP 1 (stress‐granules assembly factor) is involved in neuronal plasticity and is induced in Alzheimer's disease. We immunopurified a stable complex containing G3 BP 1 from mouse brain and performed high‐throughput sequencing and cross‐linking immunoprecipitation to identify the associated RNA s. The G3 BP ‐complex contained the deubiquitinating protease USP 10, Ct BP 1 and the RNA ‐binding proteins Caprin‐1, G3 BP 2a and splicing factor proline and glutamine rich, or PSF . The G3 BP ‐complex binds preferentially to transcripts that retain introns, and to non‐coding sequences like 3’‐untranslated region and long non‐coding RNA s. Specific transcripts with retained introns appear to be enriched in the cerebellum compared to the rest of the brain and G3 BP 1 depletion decreased this intron retention in the cerebellum of G3 BP 1 knockout mice. Among the enriched transcripts, we found an overrepresentation of genes involved in synaptic transmission, especially glutamate‐related neuronal transmission. Notably, G3 BP 1 seems to repress the expression of the mature Grm5 (metabotropic glutamate receptor 5) transcript, by promoting the retention of an intron in the immature transcript in the cerebellum. Our results suggest that G3 BP is involved in a new functional mechanism to regulate non‐coding RNA s including intron‐retaining transcripts, and thus have broad implications for neuronal gene regulation, where intron retention is widespread.