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Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription by Kristina Žumer; Ana Plemenitaš; Kalle Saksela; B. Matija Peterlin is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription about?

Autoimmune regulator (AIRE) is a transcription factor that induces the expression of a large subset of otherwise strictly tissue restricted antigens in medullary thymic epithelial cells, thereby enabling their presentation to developing T cells for negative selection. Mutations in __AIRE__ lead to autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare monogenetic disease. Although it has been reported that AIRE interacts with proteins involved in nuclear transport, DNA-damage response, chromatin remodeling, transcription and pre-mRNA-splicing, the precise mechanism of AIRE-induced tissue restricted antigen expression has remained elusive. In this study, we investigated an APECED patient mutation that causes the loss of the extreme C-terminus of AIRE and found that this mutant protein is transcriptionaly inactive. When tethered heterologously to DNA, this domain could stimulate transcription and splicing by itself. Moreover, the loss of this C-terminus disrupted interactions with the positive transcription elongation factor b (P-TEFb). Via P-TEFb, AIRE increased levels of RNA polymerase II on and enhanced pre-mRNA splicing of heterologous and endogenous targ

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Author

Kristina Žumer; Ana Plemenitaš; Kalle Saksela; B. Matija Peterlin

Publisher

Oxford University Press (OUP)

Published

2011

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)