Involvement of RNA Polymerase III in Immune Responses

Molecular and Cellular Biology
Damian GraczykKevin M Ryan

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 i...Continue Reading

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Citations

Apr 10, 2016·The FEBS Journal·Niklas A HoffmannChristoph W Müller
Aug 29, 2017·Nature Cell Biology·Evangelos GiampazoliasStephen W G Tait
Jul 19, 2019·Immunology·Jasneet Kaur KhalsaGopalakrishnan Aneeshkumar Arimbasseri
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Oct 30, 2019·Molecular and Cellular Biology·Aneta JurkiewiczDamian Graczyk
Jan 11, 2019·International Journal of Oncology·Kentaro HokonoharaMasaki Mori
Feb 23, 2020·Cancer Immunology Research·Katie E HurstJessica E Thaxton
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Jun 23, 2021·JCI Insight·Kazufumi MatsushitaStephen J Galli
Aug 10, 2021·F1000Research·Rafael Sebastián Fort, María Ana Duhagon

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