Reactome | Transcriptional regulation by small RNAs

Transcriptional regulation by small RNAs

Stable Identifier

R-HSA-5578749

DOI

10.3180/R-HSA-5578749.8

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Transcriptional regulation by small RNAs

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Recent evidence indicates that small RNAs participate in transcriptional regulation in addition to post-transcriptional silencing. Components of the RNAi machinery (ARGONAUTE1 (AGO1, EIF2C1), AGO2 (EIF2C2), AGO3 (EIF2C3), AGO4 (EIF2C4), TNRC6A, and DICER) are observed associated with microRNAs (miRNAs) in both the cytosol and the nucleus (Robb et al. 2005, Weinmann et al. 2009, Doyle et al. 2013, Nishi et al. 2013, Gagnon et al. 2014). The AGO:miRNA complexes are imported into the nucleus by IMPORTIN-8 (IPO8, IMP8, RANBP8) and also by an unknown importin while associated with the nuclear shuttling protein TNRC6A (reviewed in Schraivogel and Meister 2014).
Within the nucleus, AGO2, TNRC6A, and DICER may associate in a complex (Gagnon et al. 2014). Nuclear AGO1 and AGO2 in complexes with small RNAs are observed to activate transcription (RNA activation, RNAa) or repress transcription (Transcriptional Gene Silencing, TGS) of genes that contain sequences matching the small RNAs (reviewed in Malecova and Morris 2010, Huang and Li 2012, Gagnon and Corey 2012, Huang and Li 2014, Salmanidis et al. 2014, Stroynowska-Czerwinska et al. 2014). TGS is associated with methylation of cytosine in DNA and methylation of histone H3 at lysine-9 and lysine-27 (Castanotto et al. 2005, Suzuki et al. 2005, Kim et al. 2006, Weinberg et al. 2006, Kim et al. 2008, reviewed in Malecova and Morris 2010, Li et al. 2014); RNAa is associated with methylation of histone H3 at lysine-4 (Huang et al. 2012, reviewed in Li et al. 2014). Small RNAs in the nucleus have also been shown to play roles in alternative splicing (Liu et al., 2012, Ameyar-Zazoua et al., 2012) and DNA damage repair (Wei et al., 2012; Francia et al., 2012). Nevertheless, elucidation of the detailed mechanisms of small RNA action requires further research.

Literature References

PubMed ID	Title	Journal	Year
24384674	Demystifying the nuclear function of Argonaute proteins Huang, V, Li, LC	RNA Biol	2014
16936726	Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells Kim, DH, Villeneuve, LM, Morris, KV, Rossi, JJ	Nat Struct Mol Biol	2006
18852463	MicroRNA-directed transcriptional gene silencing in mammalian cells Kim, DH, Saetrom, P, Snøve, O, Rossi, JJ	Proc. Natl. Acad. Sci. U.S.A.	2008
22961379	Argonaute proteins couple chromatin silencing to alternative splicing Ameyar-Zazoua, M, Rachez, C, Souidi, M, Robin, P, Fritsch, L, Young, R, Morozova, N, Fenouil, R, Descostes, N, Andrau, JC, Mathieu, J, Hamiche, A, Ait-Si-Ali, S, Muchardt, C, Batsché, E, Harel-Bellan, A	Nat. Struct. Mol. Biol.	2012
22722852	Site-specific DICER and DROSHA RNA products control the DNA-damage response Francia, S, Michelini, F, Saxena, A, Tang, D, de Hoon, M, Anelli, V, Mione, M, Carninci, P, d'Adda di Fagagna, F	Nature	2012
23150874	Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus Nishi, K, Nishi, A, Nagasawa, T, Ui-Tei, K	RNA	2013
15643423	Specific and potent RNAi in the nucleus of human cells Robb, GB, Brown, KM, Khurana, J, Rana, TM	Nat. Struct. Mol. Biol.	2005
16373483	The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells Weinberg, MS, Villeneuve, LM, Ehsani, A, Amarzguioui, M, Aagaard, L, Chen, ZX, Riggs, AD, Rossi, JJ, Morris, KV	RNA	2006
22445173	A role for small RNAs in DNA double-strand break repair Wei, W, Ba, Z, Gao, M, Wu, Y, Ma, Y, Amiard, S, White, CI, Rendtlew Danielsen, JM, Yang, YG, Qi, Y	Cell	2012
15963934	Short hairpin RNA-directed cytosine (CpG) methylation of the RASSF1A gene promoter in HeLa cells Castanotto, D, Tommasi, S, Li, M, Li, H, Yanow, S, Pfeifer, GP, Rossi, JJ	Mol. Ther.	2005
22336708	miRNA goes nuclear Huang, V, Li, LC	RNA Biol	2012
25131816	Import routes and nuclear functions of Argonaute and other small RNA-silencing proteins Schraivogel, D, Meister, G	Trends Biochem. Sci.	2014
24468964	The panorama of miRNA-mediated mechanisms in mammalian cells Stroynowska-Czerwinska, A, Fiszer, A, Krzyzosiak, WJ	Cell. Mol. Life Sci.	2014
24388755	RNAi factors are present and active in human cell nuclei Gagnon, KT, Li, L, Chu, Y, Janowski, BA, Corey, DR	Cell Rep	2014
24680896	Direct transcriptional regulation by nuclear microRNAs Salmanidis, M, Pillman, K, Goodall, G, Bracken, C	Int. J. Biochem. Cell Biol.	2014
22283730	Argonaute and the nuclear RNAs: new pathways for RNA-mediated control of gene expression Gagnon, KT, Corey, DR	Nucleic Acid Ther	2012
23882114	The double-stranded RNA binding domain of human Dicer functions as a nuclear localization signal Doyle, M, Badertscher, L, Jaskiewicz, L, Güttinger, S, Jurado, S, Hugenschmidt, T, Kutay, U, Filipowicz, W	RNA	2013
21948593	Expanding the action of duplex RNAs into the nucleus: redirecting alternative splicing Liu, J, Hu, J, Corey, DR	Nucleic Acids Res.	2012
20373265	Transcriptional gene silencing through epigenetic changes mediated by non-coding RNAs Malecová, B, Morris, KV	Curr. Opin. Mol. Ther.	2010
22053081	Upregulation of Cyclin B1 by miRNA and its implications in cancer Huang, V, Place, RF, Portnoy, V, Wang, J, Qi, Z, Jia, Z, Yu, A, Shuman, M, Yu, J, Li, LC	Nucleic Acids Res.	2012
19771207	Prolonged transcriptional silencing and CpG methylation induced by siRNAs targeted to the HIV-1 promoter region Suzuki, K, Shijuuku, T, Fukamachi, T, Zaunders, J, Guillemin, G, Cooper, D, Kelleher, A	J RNAi Gene Silencing	2005