Transcriptional activation by bidirectional RNA polymerase II elongation over a silent promoter

Transcriptional interference denotes negative cis effects between promoters. Here, we show that promoters can also interact positively. Bidirectional RNA polymerase II (Pol II) elongation over the silent human endogenous retrovirus ( HERV)-K18 promoter ( representative of 2.5 +/- 10(3) similar promoters genome-wide) activates transcription. In tandem constructs, an upstream promoter activates HERV-K18 transcription. This is abolished by inversion of the upstream promoter, or by insertion of a poly( A) signal between the promoters; transcription is restored by poly( A) signal mutants. TATA-box mutants in the upstream promoter reduce HERV-K18 transcription. Experiments with the same promoters in a convergent orientation produce similar effects. A small promoter deletion partially restores HERV-K18 activity, consistent with activation resulting from repressor repulsion by the elongating Pol II. Transcriptional elongation over this class of intragenic promoters will generate co-regulated sense - antisense transcripts, or, alternatively initiating transcripts, thus expanding the diversity and complexity of the human transcriptome

The proteolytic activity of the paracaspase MALT1 is key in T cell activation

The paracaspase MALT1 is pivotal in antigen receptor-mediated lymphocyte activation and lymphomagenesis. MALT1 contains a caspase-like domain, but it is unknown whether this domain is proteolytically active. Here we report that MALT1 had arginine-directed proteolytic activity that was activated after T cell stimulation, and we identify the signaling protein Bcl-10 as a MALT1 substrate. Processing of Bcl-10 after Arg228 was required for T cell receptor-induced cell adhesion to fibronectin. In contrast, MALT1 activity but not Bcl-10 cleavage was essential for optimal activation of transcription factor NF-kappaB and production of interleukin 2. Thus, the proteolytic activity of MALT1 is central to T cell activation, which suggests a possible target for the development of immunomodulatory or anticancer drug