RGD Reference Report - Alternative splicing of iodothyronine deiodinases in pituitary adenomas. Regulation by oncoprotein SF2/ASF. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Alternative splicing of iodothyronine deiodinases in pituitary adenomas. Regulation by oncoprotein SF2/ASF.

Authors: Piekielko-Witkowska, A  Kedzierska, H  Poplawski, P  Wojcicka, A  Rybicka, B  Maksymowicz, M  Grajkowska, W  Matyja, E  Mandat, T  Bonicki, W  Nauman, P 
Citation: Piekielko-Witkowska A, etal., Biochim Biophys Acta. 2013 Jun;1832(6):763-72. doi: 10.1016/j.bbadis.2013.02.013. Epub 2013 Feb 24.
RGD ID: 11038736
Pubmed: PMID:23462647   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbadis.2013.02.013   (Journal Full-text)

Pituitary tumors belong to the group of most common neoplasms of the sellar region. Iodothyronine deiodinase types 1 (DIO1) and 2 (DIO2) are enzymes contributing to the levels of locally synthesized T3, a hormone regulating key physiological processes in the pituitary, including its development, cellular proliferation, and hormone secretion. Previous studies revealed that the expression of deiodinases in pituitary tumors is variable and, moreover, there is no correlation between mRNA and protein products of the particular gene, suggesting the potential role of posttranscriptional regulatory mechanisms. In this work we hypothesized that one of such mechanisms could be the alternative splicing. Therefore, we analyzed expression and sequences of DIO1 and DIO2 splicing variants in 30 pituitary adenomas and 9 non-tumorous pituitary samples. DIO2 mRNA was expressed as only two mRNA isoforms. In contrast, nine splice variants of DIO1 were identified. Among them, five were devoid of exon 3. In silico sequence analysis of DIO1 revealed multiple putative binding sites for splicing factor SF2/ASF, of which the top-ranked sites were located in exon 3. Silencing of SF2/ASF in pituitary tumor GH3 cells resulted in change of ratio between DIO1 isoforms with or without exon 3, favoring the expression of variants without exon 3. The expression of SF2/ASF mRNA in pituitary tumors was increased when compared with non-neoplastic control samples. In conclusion, we provide a new mechanism of posttranscriptional regulation of DIO1 and show deregulation of DIO1 expression in pituitary adenoma, possibly resulting from disturbed expression of SF2/ASF.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SRSF1HumanPituitary Neoplasms  IEP mRNA:increased expression:pituitary gland (human)RGD 
Srsf1RatPituitary Neoplasms  ISOSRSF1 (Homo sapiens)mRNA:increased expression:pituitary gland (human)RGD 
Srsf1MousePituitary Neoplasms  ISOSRSF1 (Homo sapiens)mRNA:increased expression:pituitary gland (human)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Srsf1Ratalternative mRNA splicing, via spliceosome  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Srsf1  (serine and arginine rich splicing factor 1)

Genes (Mus musculus)
Srsf1  (serine and arginine-rich splicing factor 1)

Genes (Homo sapiens)
SRSF1  (serine and arginine rich splicing factor 1)


Additional Information