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Article

m6A modification of mutant huntingtin RNA promotes the biogenesis of pathogenic huntingtin transcripts.

EMBO reports - 1 Nov 2024

Pupak Anika, Rodríguez-Navarro Irene, Sathasivam Kirupa, Singh Ankita, Essmann Amelie, Del Toro Daniel, Ginés Silvia, Mouro Pinto Ricardo, Bates Gillian P, Vang Ørom Ulf Andersson, Martí Eulàlia, Brito Verónica

Abstract excerpt

In Huntington's disease (HD), aberrant processing of huntingtin (HTT) mRNA produces HTT1a transcripts that encode the pathogenic HTT exon 1 protein. The mechanisms behind HTT1a production are not fully understood. Considering the role of m6A in RNA processing and splicing, we investigated its involvement in HTT1a generation. Here, we show that m6A methylation is increased before the cryptic poly(A) sites (IpA1...

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Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

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Source

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Identifiers

PMID: 39394467
DOI: 10.1038/s44319-024-00283-7
PMCID: PMC11549361

Genes

HTT
METTL3
ALKBH5

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 8 Sept 2026.

Related research

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Research trail→

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m6A modification of mutant huntingtin RNA promotes the biogenesis of pathogenic huntingtin transcripts.PMID 39394467Read ↗

m6A RNA modification of m <i>Htt</i> intron 1 regulates the generation of <i>Htt1a</i> in Huntington’s DiseaseSemantic proximity Read ↗

Aberrant splicing in Huntington’s disease via disrupted TDP-43 activity accompanied by altered m6A RNA modificationSemantic proximity Read ↗

PRMT5 is required for full-length <i>HTT</i> expression by repressing multiple proximal intronic polyadenylation sitesSemantic proximity Read ↗

Targeted 3’-end RNA sequencing uncovers cryptic polyadenylation in Huntington’s disease linked to somatic instability and CAG repeat puritySemantic proximity Read ↗

The m6A RNA methylation exerts a neuroprotective function by regulating the expression of α-synucleinSemantic proximity Read ↗

METTL3-IGF2BP3 m⁶A axis drives mutant huntingtin stability and neurodegeneration in Huntington’s diseaseSemantic proximity Read ↗

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