Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.
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http://dx.doi.org/10.1038/s41598-017-12955-7 | DOI Listing |
NPJ Syst Biol Appl
January 2025
The Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, 94608, USA.
Genome-scale metabolic models (GSMM) are commonly used to identify gene deletion sets that result in growth coupling and pairing product formation with substrate utilization and can improve strain performance beyond levels typically accessible using traditional strain engineering approaches. However, sustainable feedstocks pose a challenge due to incomplete high-resolution metabolic data for non-canonical carbon sources required to curate GSMM and identify implementable designs. Here we address a four-gene deletion design in the Pseudomonas putida KT2440 strain for the lignin-derived non-sugar carbon source, p-coumarate (p-CA), that proved challenging to implement.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Pharmacology, Republic of Korea; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 440-746, Republic of Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea. Electronic address:
ZNF398/ZER6 belongs to the Krüppel-associated box (KRAB) domain-containing zinc finger proteins (K-ZNFs), the largest family of transcriptional repressors in higher organisms. ZER6 exists in two isoforms, p52 and p71, generated through alternative splicing. Our investigation revealed that p71-ZER6 is abundantly expressed in the stomach, kidney, liver, heart, and brown adipose tissue, while p52-ZER6 is predominantly found in the stomach and brain.
View Article and Find Full Text PDFResusc Plus
January 2025
Department of Paediatrics, Division of Paediatric Critical Care, CHEO, 401 Smyth Rd, Ottawa, Ontario K1H 8L1, Canada.
Background: Self-directed training has been recognized as a reasonable alternative to traditional instructor-led formats to teach laypeople Basic Life Support (BLS). Virtual tools can facilitate high-quality self-directed resuscitation education; however, their role in teaching paediatric BLS remains unclear due to limited empiric evaluation and suboptimal design of existing tools.
Aim: We describe the development and evaluation of a virtual simulation game (VSG) designed to teach high-quality paediatric BLS using a self-directed, online format with integrated deliberate practice and feedback.
Int J Biol Macromol
January 2025
CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; RISE-Health, Departamento de Química, Faculdade de Ciências, Universidade da Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001 Covilhã, Portugal; Departamento de Química, Universidade da Beira Interior, Rua Marquês de Ávila e Bolama, 6201-001 Covilhã, Portugal. Electronic address:
Understanding the mechanisms of carcinogenesis is essential to combat cancer. The search for alternative targets for anticancer therapy has gained interest, particularly when focused on upstream pathways. This strategy is particularly relevant when the encoded target proteins are known - or believed - to be "undruggable", as has been reported for the B-MYB oncogene.
View Article and Find Full Text PDFGenes Dev
December 2024
Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA
Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs, yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.
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