MCB Accepts, published online ahead of print on 19 October 2009

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Mol. Cell. Biol. doi:10.1128/MCB.00884-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

TLS inhibits RNA polymerase III transcription

Adelene Y. Tan and James L. Manley^*

Department of Biological Sciences, Columbia University, New York, NY 10027

^* To whom correspondence should be addressed. Email: jlm2{at}columbia.edu.

RNA transcription by all the three RNA polymerases is tightly controlled, and loss of regulation can lead for example to cellular transformation and cancer. While most transcription factors act specifically with one polymerase, a small number have been shown to affect more than one to coordinate overall levels of transcription in cells. Here we show that TLS (translocated in liposarcoma), a protein originally identified as the product of a chromosomal translocation and which associates with both RNA polymerase (RNAP) II and the spliceosome, also represses transcription by RNAP III. TLS was found to repress transcription from all three classes of RNAP III promoters in vitro, and to associate with RNAP III genes in vivo, perhaps via a direct interaction with the pan-specific transcription factor TATA-binding protein (TBP). Depletion of TLS by siRNA in HeLa cells resulted in increased steady-state levels of RNAP III transcripts as well as increased RNAP III and TBP occupancy at RNAP III-transcribed genes. Conversely, overexpression of TLS decreased accumulation of RNAP III transcripts. These unexpected findings indicate that TLS regulates both RNAP II and III, and supports the possibility that cross-regulation between RNA polymerases is important in maintaining normal cell growth.