The Zap1 transcriptional activator negatively regulates translation of the RTC4 mRNA through the use of alternative 5' transcript leaders.

Mol Microbiol

Département de Biochimie, Faculté de médecine et des sciences de la santé, Pavillon Z-8, 3201, Jean Mignault, Sherbrooke, QC J1E 4K8, Canada.

Published: December 2017


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

The zinc-responsive transcription activator Zap1 plays a central role in zinc homeostasis in the budding yeast Saccharomyces cerevisiae. In zinc-deficient cells, Zap1 binds to zinc responsive elements in target gene promoters and activates gene expression. In most cases, Zap1-dependent gene activation results in increased levels of mRNAs and proteins. However, Zap1-dependent activation of RTC4 results in increased levels of the RTC4 mRNA and decreased levels of the Rtc4 protein. This atypical regulation results from Zap1-mediated changes in the transcriptional start site for RTC4 and the production of a RTC4 transcript with a longer 5' leader. This long RTC4 transcript contains small upstream open reading frames that prevent translation of the downstream RTC4 ORF. The new studies with Zap1 highlight how a transcriptional activator can facilitate decreased protein expression.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705029PMC
http://dx.doi.org/10.1111/mmi.13856DOI Listing

Publication Analysis

Top Keywords

transcriptional activator
8
rtc4
8
rtc4 mrna
8
increased levels
8
levels rtc4
8
rtc4 transcript
8
zap1
4
zap1 transcriptional
4
activator negatively
4
negatively regulates
4

Similar Publications

Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer's disease mouse model.

Acta Neuropathol Commun

September 2025

Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.

Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.

View Article and Find Full Text PDF

Background: Stroke-prone spontaneously hypertensive rats (SHRSP) exhibit slow-twitch muscle-specific hypotrophy compared with normotensive Wistar-Kyoto rats (WKY). Because slow-twitch muscles are prone to disuse atrophy, SHRSP may experience both disuse atrophy and impaired recovery from it. This study investigated the response of SHRSP to disuse atrophy and subsequent recovery, using WKY as a control.

View Article and Find Full Text PDF

Whole blood (WB) transcriptomics offers a minimal-invasive method to assess patients' immune system. This study aimed to identify transcriptional patterns in WB associated with clinical outcomes in patients treated with immune checkpoint inhibitors (ICIs). We performed RNA-sequencing on pre-treatment WB samples from 145 patients with advanced cancer.

View Article and Find Full Text PDF

RNF128 regulates the adaptive metabolic response to fasting by modulating PPARα function.

Cell Death Differ

September 2025

Graduate Institute of Physiology, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan, Republic of China.

Peroxisome proliferator-activated receptor alpha (PPARα) is a crucial transcriptional factor that regulates fatty acid β-oxidation and ketogenesis in response to fasting. However, the mechanisms underlying PPARα function remain unclear. This study identified a novel PPARα-binding protein-RING finger protein 128 (RNF128)-that facilitates PPARα polyubiquitination, resulting in the degradation and suppression of PPARα function during fasting.

View Article and Find Full Text PDF

The anti-HER2 antibody‒drug conjugate (ADC) DS-8201 presents new hope for patients with advanced HER2-positive tumors. Its clinical application, however, is hindered by serious adverse reactions and reduced efficacy following long-term treatment. In this study, we investigated the factors influencing the sensitivity of DS-8201 and developed effective combination regimens to optimize its therapeutic efficacy.

View Article and Find Full Text PDF