Molecular genetics and genomics : MGGOct 14, 2026

HuR influences disease-related gene changes linked to Alzheimer's, including MAPT

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 16, 2026

Abstract

HuR is identified as a novel repressor of MAPT exon 10 splicing.

Dysregulation of MAPT exon 10 splicing is associated with tauopathies, including Alzheimer's disease.
The RRM1 domain of HuR is critical for its inhibitory effect on splicing.
HuR binds to specific regions in the MAPT gene alongside several other proteins.
The expression of HuR negatively correlates with the expression of FUBP1, KHSRP, hnRNPD, and TIAL1.
HuR regulates the expression and splicing of genes involved in autophagy and apoptosis, which are pathways affected in Alzheimer's disease.

Simplified

Alternative splicing of MAPT exon 10 generates 4R- and 3R-Tau isoforms, and its dysregulation is associated with tauopathies including Alzheimer's disease (AD), for which effective treatments remain lacking. Here, we identify HuR as a novel repressor of MAPT exon 10 alternative splicing. Mechanistically, the RRM1 domain of HuR is critical for mediating its splicing inhibitory effect. HuR binds to the U-rich region downstream of intron 9 in MAPT together with FUBP1, KHSRP, hnRNPD, hnRNPAB, hnRNPDL, and TIAL1. The expression of HuR shows a negative association with that of FUBP1, KHSRP, hnRNPD, and TIAL1. Finally, we demonstrate that HuR regulates the expression and alternative splicing of genes involved in autophagy and apoptosis, pathways dysregulated in AD. Collectively, these findings establish HuR as a regulator of AD-relevant transcriptomic networks and provide a mechanistic basis for exploring HuR-targeted strategies in AD.

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HuR influences disease-related gene changes linked to Alzheimer's, including MAPT

Abstract

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