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Three distinct messenger RNAs can encode the human immunosuppressant-binding protein FKBP12
D A Peattie1, K Hsiao, M Benasutti
1Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139-4211.
Gene
|December 15, 1994
Summary
Three human FKBP12 messenger RNA transcripts (FKBP12A, 12B, 12C) encode the same protein but differ in their 3' untranslated regions. T-cell activation increases FKBP12A and 12B mRNA levels.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- FKBP12 is an 11.8-kDa protein that binds immunosuppressants FK506 and rapamycin.
- FKBP12-FK506 complexes inhibit calcineurin, interfering with T-lymphocyte signal transduction.
Purpose of the Study:
- To investigate the molecular mechanisms underlying human FKBP12 expression.
- To identify distinct transcripts encoding FKBP12 and their regulation.
Main Methods:
- Analysis of human FKBP12 cDNAs and gene.
- Characterization of transcript variants (FKBP12A, 12B, 12C).
- Assessment of mRNA abundance in activated T-cells and various human tissues.
Main Results:
- Three distinct transcripts (FKBP12A, 12B, 12C) encode human FKBP12, differing in 3' untranslated regions but sharing identical open reading frames.
- Transcripts originate from four or five exons via differential splicing and polyadenylation.
- FKBP12A and 12B mRNA levels increase upon T-cell activation, suggesting increased demand.
- These transcripts are found in diverse human tissues.
Conclusions:
- Differential transcript usage generates multiple FKBP12 mRNA variants.
- T-cell activation upregulates specific FKBP12 transcripts.
- FKBP12 and its mRNAs may play roles in various physiological processes across different cell types.