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The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock

Abstract

Cells respond to changes in environmental conditions via orchestrated modifications in gene expression. For example, in response to heat shock, cells execute a program of gene-specific transcriptional activation and repression. Although the activation of genes upon heat shock has been widely studied, the mechanism of mRNA transcriptional repression upon heat shock is unexplained. Here we show that during the heat shock response in mouse cells, a small noncoding RNA polymerase III transcript, B2 RNA, associates with RNA polymerase II and represses transcription of specific mRNA genes. These studies define a unique transcriptional regulatory mechanism involving an RNA regulator and reveal how mRNA transcription is repressed upon heat shock. Moreover, we identify a function for B2 RNA, which is transcribed from short interspersed elements that are abundant in the mouse genome and historically considered to be 'junk DNA.'

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Figure 1: After heat shock in NIH 3T3 cells, nuclear B1 and B2 RNA levels decreased and nuclear actin and hexokinase II mRNA levels increased concomitantly.
Figure 2: Ongoing Pol III transcription is required for the decrease in mRNA transcription after heat shock.
Figure 3: B2 RNA inhibits Pol II transcription in vitro.
Figure 4: B2 RNA is required for repression of mRNA transcription upon heat shock in mouse cells.
Figure 5: B2 RNA associates with Pol II in response to heat shock.
Figure 6: Model illustrating the mechanism of transcriptional repression after heat shock in mouse cells.

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Acknowledgements

We thank E. Podell for group I intron RNA and S.K. Galasinski for technical assistance. This research was supported by research project grant RPG-00-271-01-MGO from the American Cancer Society; public health service grant GM-68414 from the US National Institutes of Health; and a Pew Scholarship in the Biomedical Sciences to J.A.G.

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Correspondence to James A Goodrich or Jennifer F Kugel.

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Allen, T., Von Kaenel, S., Goodrich, J. et al. The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock. Nat Struct Mol Biol 11, 816–821 (2004). https://doi.org/10.1038/nsmb813

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