Involvement of RNA polymerase III in immune responses

Graczyk, D., White, R. and Ryan, K. (2015) Involvement of RNA polymerase III in immune responses. Molecular and Cellular Biology, 35(10), pp. 1848-1859. (doi:10.1128/MCB.00990-14) (PMID:25776554)

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Abstract

Inflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis, and metastasis. Enhanced cytokine production by TAMs is tightly coupled with protein synthesis. In turn, translation of proteins depends on tRNAs, short abundant transcripts that are made by RNA polymerase III (Pol III). Here, we connect these facts by showing that stimulation of mouse macrophages with lipopolysaccharides (LPS) from the bacterial cell wall causes transcriptional upregulation of tRNA genes. The transcription factor NF-κB is a key transcription factor mediating inflammatory signals, and we report that LPS treatment causes an increased association of the NF-κB subunit p65 with tRNA genes. In addition, we show that p65 can directly associate with the Pol III transcription factor TFIIIB and that overexpression of p65 induces Pol III-dependent transcription. As a consequence of these effects, we show that inhibition of Pol III activity in macrophages restrains cytokine secretion and suppresses phagocytosis, two key functional characteristics of these cells. These findings therefore identify a radical new function for Pol III in the regulation of macrophage function which may be important for the immune responses associated with both normal and malignant cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ryan, Professor Kevin and White, Prof Robert and Graczyk, Dr Damian
Authors: Graczyk, D., White, R., and Ryan, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Molecular and Cellular Biology
Publisher:American Society for Microbiology
ISSN:0270-7306
ISSN (Online):1098-5549
Copyright Holders:Copyright © 2015 American Society for Microbiology
First Published:First published in Molecular and Cellular Biology 35(10):1848-1859
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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