ArticleRNA biology2015
Structural determinants for alternative splicing regulation of the MAPT pre-mRNA.
Article in RNA biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- mRNA Isoforms and Variants in Health and Disease.International journal of molecular sciences · 2025Review
- Development of MAPT S305 mutation human iPSC lines exhibiting elevated 4R tau expression and functional alterations in neurons and astrocytes.Cell reports · 2024Article
- The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- How does precursor RNA structure influence RNA processing and gene expression?Bioscience reports · 2023Review
- Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022Review
- Article
- RNA Secondary Structure-Based Design of Antisense Peptide Nucleic Acids for Modulating Disease-Associated Aberrant Tau Pre-mRNA Alternative Splicing.Molecules (Basel, Switzerland) · 2019Article
- Guidelines for SHAPE Reagent Choice and Detection Strategy for RNA Structure Probing Studies.Biochemistry · 2019Article
- The RNA encoding the microtubule-associated protein tau has extensive structure that affects its biology.PloS one · 2019Article
- RNA Splicing and Disease: Animal Models to Therapies.Trends in genetics : TIG · 2019Review
- Influence of mismatched and bulged nucleotides on SNP-preferential RNase H cleavage of RNA-antisense gapmer heteroduplexes.Scientific reports · 2017Article
- Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans.Aging cell · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative splicing at the MAPT gene exon 10 yields similar levels of the 3R and 4R tau protein isoforms. (1) The presence of mutations, particularly in exon 10 and intron 10-11, changes the quantity of tau isoforms. Domination each of the isoform yields tau protein aggregation and frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Here, we report for the first time the secondary structure of the 194/195 nucleotide region for the wild type (WT) and 10 mutants of the MAPT gene pre-mRNA determined using both chemical and microarray mapping. Thermodynamic analyses indicate that single nucleotide mutations in the splicing regulatory element (SRE) that form a hairpin affect its stability by up to 4 and 7 kcal/mol. Moreover, binding the regulatory hairpin of small molecule ligands (neomycin, kanamycin, tobramycin and mitoxantrone) enhance its stability depending on the nature of the ligands and the RNA mutations. Experiments using the cos-7 cell line indicate that the presence of ligands and modified antisense oligonucleotides affect the quantity of 3R and 4R isoforms. This finding correlates with the thermodynamic stability of the regulatory hairpin. An alternative splicing regulation mechanism for exon 10 is postulated based on our experimental data and on published data.
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