Acts upstream of or within, negative effect
Overview
The acts upstream of or within, negative effect annotation relation is used when the experimental evidence is not sufficient to determine the mechanism relating a gene product's activity to a biological process. However, the observed experimental outcome indicates that, ultimately, the gene product's activity has a negative effect on the process. Annotations using this relation often come from mutant phenotypes for which further characterization has not been performed, but the authors wish to report the effect that the gene has on a process.
Definition
Child Terms
Examples of Usage
- The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations.
- Overexpression of miR-462 and miR-731 represses cell proliferation through blocking cell cycle progress of DNA replication, and induces apoptosis.
- Summary of the paper:
INTRO
- The transcription factor HIF1-alpha is hydroxylated at proline residues under normal oxygen conditions ("normoxia"), which targets it for proteosomal degradation. Hence under normal conditions its half life is very short.
- Under limiting O2 conditions, the prolyl hydroxylase activity is reduced, and HIF1-alpha is stabilized, and interacts with HIF1-beta.
- The HIF1-alpha/beta dimer activates hundreds of genes involved in hypoxia adaptation via their DNA binding transcription activator activity, binding to HRE (hypoxia-responsive elements)
- Hundreds of genes are also down-regulated in a HIF1-dependent manner, but without direct HIF1-promoter binding
RESULTS
- Deep sequencing of small RNA libraries identified 129 and and 212 novel miRNAs under normoxia and hypoxia conditions, 102 of which in common to both sets (NOTE: these miRNAs were not further studied).
- To identify known miRNA, the authors looked into the miRBase, that contained 247 known miRNAs. Seven differentially regulated known
miRNAs were identified: 5 upregulated and 2 downregulated (Table 3).
- dre-miR-462
- miR-462 'acts upstream of or within, negative effect' cell proliferation (or DNA replication?)
Quality Control Checks
Relations Ontology
acts upstream of or within, negative effect
Review Status
Last reviewed: March 9, 2018