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Published on: June 20, 2018
Atypical CTSK transcripts and ARNT transcription read-through into CTSK
Fabienne S Giraudeau1, Jean-Philippe Walhin, Paul R Murdock
1Department of Discovery Genetics, GlaxoSmithKline Research and Development, New Frontiers Science Park, Harlow, UK.
The aryl hydrocarbon receptor nuclear translocator (ARNT) gene may extend into the cathepsin K (CTSK) gene, potentially reducing CTSK expression. Novel CTSK transcripts with alternative splicing and initiation sites were also identified.
Area of Science:
- Genetics
- Molecular Biology
- Gene Regulation
Background:
- The aryl hydrocarbon receptor nuclear translocator (ARNT) and cathepsin K (CTSK) genes are located closely on human chromosome 1.
- Their proximity suggests potential regulatory interactions between ARNT and CTSK gene expression.
Purpose of the Study:
- To investigate the transcriptional relationship between ARNT and CTSK.
- To identify novel CTSK transcripts and their regulatory mechanisms.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) to detect overlapping transcripts.
- Quantitative RT-PCR to assess ARNT expression within CTSK introns.
- Sequence analysis of expressed sequence tags (ESTs) and RT-PCR products.
Main Results:
- Evidence of ARNT transcripts extending into the CTSK gene, up to intron 3.
- ARNT read-through may negatively impact CTSK transcript levels.
- Identification of novel CTSK transcripts with alternative 5' splicing and/or 5' extension.
- Discovery of a cryptic alternative promoter upstream of the known CTSK promoter, possibly within the ARNT 3' UTR.
Conclusions:
- ARNT read-through transcription is a significant finding impacting CTSK gene expression.
- Alternative splicing and promoter usage contribute to CTSK transcript diversity.
- These findings reveal complex gene regulation mechanisms for closely located genes.
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