Alternative production of pro-death Bax∆2 protein via ribosomal frameshift in Alzheimer's disease.

ABSTRACT: Pro-death Bax family member, Bax∆2, forms protein aggregates in Alzheimer's disease neurons and causes stress granule-mediated neuronal death. Production of Bax∆2 originated from two events: alternative splicing of Bax exon 2 and a microsatellite mutation (a deletion from poly guanines, G8 to G7). Each event alone leads to a reading frameshift and premature termination. While Bax exon 2 alternative splicing is common in Alzheimer's brains, the G7 mutation is not, which is inconsistent with the high Bax∆2 protein levels detected in clinical samples. Here, we report an alternative mechanism to produce Bax∆2 protein in the absence of the G7 mutation. Using dual-tag systems, we showed that a ribosomal frameshift (RFS) can compensate the lack of G7 mutation in translating Bax∆2 protein. Intrigu

SUBMITTER: Yao Q 

PROVIDER: S-EPMC11549088 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature