What is Gene Ontology?
Gene Ontology refers to the collection of data and knowledge for a particular gene and its function across several different species. Gene ontology can be used by scientists to collaborate and create a universal framework of the current state of a gene. Gene ontology can characterize a particular gene by describing the current knowledge of its: Cellular Component, Molecular Function, and Biological Process [1].
Cellular Component
The cellular component of a gene refers to the specific locations the product of the gene will carry its function.
Molecular Function
The molecular function of a gene refers to the specific functions and activities that are carried out by the products of the gene.
Biological Process
The biological process of a gene refers to the larger cellular processes that are enabled by the functions or activities carried out by the gene products.
Cellular Component
The cellular component of a gene refers to the specific locations the product of the gene will carry its function.
Molecular Function
The molecular function of a gene refers to the specific functions and activities that are carried out by the products of the gene.
Biological Process
The biological process of a gene refers to the larger cellular processes that are enabled by the functions or activities carried out by the gene products.
DYRK1A Gene Ontology
Cellular Component
DYRK1A is located primarily in the cytosol and can also localize in the nucleolus fibrillar center. The nucleolus fibrillar center is where ribosomes are manufactured by the cell [2].
Molecular Function
DYRK1A is a dual-specificity kinase so it is capable of serine/threonine and tyrosine kinase activity [2].
Biological Process
DYRK1A is known to play a role in cell proliferation signaling pathways by regulating nuclear functions. DYRK1A is also associated with pro-survival functions by negatively regulating apoptotic processes. DYRK1A can promote cell survival by phosphorylating SIRT1 which then inhibits TP53 activity and stops apoptosis [2].
DYRK1A affects several transcription factors by regulating their nuclear localization.
Normally, transcription factors are not phosphorylated, and they can enter the nucleus, bind to the promoter and facilitate transcription of genes. In this case, genes that specifically regulate neural proliferation. This results in normal neurogenesis.
DYRK1A interacts with transcription factors to inhibit their function. DYRK1A does this by phosphorylating the transcription factor. This causes the transcription factor to no longer be able to pass the nuclear membrane. Therefore, the transcription factor can no longer bind to the promoter of genes that regulate neural proliferation. This would result in reduced neural proliferation and affect overall neural development.
Normally, transcription factors are not phosphorylated, and they can enter the nucleus, bind to the promoter and facilitate transcription of genes. In this case, genes that specifically regulate neural proliferation. This results in normal neurogenesis.
DYRK1A interacts with transcription factors to inhibit their function. DYRK1A does this by phosphorylating the transcription factor. This causes the transcription factor to no longer be able to pass the nuclear membrane. Therefore, the transcription factor can no longer bind to the promoter of genes that regulate neural proliferation. This would result in reduced neural proliferation and affect overall neural development.
Discussion
The gene ontology terms associated with DYRK1A supports that DYRK1A is involved in neural cell proliferation and possibly even cell cycle modulation in neurons. The higher dose of DYRK1A present in those affected by Down syndrome could lead to abnormal cell cycle modulation and proliferation of neurons in the brain. Continued investigation of these three gene ontology terms is necessary to determine the exact role DYRK1A has in neural cell proliferation.
References:
1. http://geneontology.org/docs/ontology-documentation/
2. https://www.proteinatlas.org/ENSG00000157540-DYRK1A
2. https://www.proteinatlas.org/ENSG00000157540-DYRK1A
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison