TDP-43 is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. In particular, TDP-43 is a splicing factor binding to the intron8/exon9 junction of the CFTR gene and to the intron2/exon3 region of the apoA-II gene. A similar pseudogene is present on chromosome 20.
TDP-43 has been shown to bind both DNA and RNA and have multiple functions in transcriptional repression, pre-mRNA splicing and translational regulation. Recent work has characterized the transcriptome-wide binding sites revealing that thousands of RNAs are bound by TDP-43 in neurons.
TDP-43 was originally identified as a transcriptional repressor that binds to chromosomally integrated trans-activation response element (TAR) DNA and represses HIV-1 transcription. It was also reported to regulate alternate splicing of the CFTR gene and the apoA-II gene.
In spinal motor neurons TDP-43 has also been shown in humans to be a low molecular weight microfilament (hNFL) mRNA-binding protein. It has also shown to be a neuronal activity response factor in the dendrites of hippocampal neurons suggesting possible roles in regulating mRNA stability, transport and local translation in neurons.
HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNAgenome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator "Tat" is dependent on an RNA regulatory element (TAR) located "downstream" (i.e. to-be transcribed at a later point in time) of the transcription initiation site.
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