Regulation of RNA Polymerase II by non-coding RNAs
In response to heat shock, cells execute a program of gene-specific transcriptional activation and repression. We have found that during the heat shock response in mouse cells, a small non-coding RNA polymerase III transcript, B2 RNA, associates with RNA polymerase II and represses transcription of specific mRNA genes. It does so by binding to core RNA polymerase II with high affinity and specificity. We have shown in vitro that B2 RNA assembles into preinitiation complexes at promoter DNA and blocks all detectable RNA synthesis. These studies define a unique transcriptional regulatory mechanism involving an RNA regulator. Moreover, they identify a function for B2 RNA, which is transcribed from short interspersed elements (SINEs) that are abundant in the mouse genome and historically considered to be 'junk DNA'. Because we are ultimately interested in understanding the regulation of human transcription, we are also identifying and studying human RNA(s) that control RNA polymerase II transcription.
Publications:
Espinoza, C.A., Goodrich, J.A., and Kugel, J.F. (2007). Characterization of the structure, function and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription. RNA. 13: 583-596.
Goodrich, J.A. and Kugel, J.F. (2006). Noncoding RNA regulators of RNA polymerase II transcription. Nature Rev. Mol. Cell Biol. 7: 612-616.
Espinoza, C.A., Allen, T.A., Hieb, A.R., Kugel, J.F., and Goodrich, J.A. (2004). B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. Nature Struct. Mol. Biol. 11: 822-829.
Allen, T.A., Von Kaenel, S., Goodrich, J.A., and Kugel, J.F. (2004). The SINE encoded mouse B2 RNA represses mRNA transcription in response to heat shock. Nature Struct. Mol. Biol. 11: 816-821.
Kugel, J.F. and Goodrich, J.A. (1998). Promoter escape limits the rate of transcription from the adenovirus major late promoter on negatively supercoiled templates. Proc. Natl. Acad. Sci. 95: 9232-9237.