Reactome | RNA polymerase II transcribes snRNA genes

RNA polymerase II transcribes snRNA genes

Stable Identifier

R-HSA-6807505

DOI

10.3180/r-hsa-6807505.1

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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RNA polymerase II transcribes snRNA genes

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Small nuclear RNAs (snRNAs) play key roles in splicing and some of them, specifically the U1 and U2 snRNAs, are encoded by multicopy snRNA gene clusters containing tandem arrays of genes, about 30 in the RNU1 cluster (Bernstein et al. 1985) and about 10-20 in the RNU2 cluster (Van Ardsell and Weiner 1984). Whereas U6 snRNA genes are transcribed by RNA polymerase III, U1,U2, U4, U4atac, U5, U11, and U12 genes are transcribed by RNA polymerase II. Transcription of the U1 and U2 genes has been most extensively studied and the other snRNA genes as well as other genes with similar promoter structures, for example the SNORD13 gene, are inferred to be transcribed by similar reactions. The snRNA genes transcribed by RNA polymerase II are distinguished from mRNA-encoding genes by the presence of a proximal sequence element (PSE) rather than a TATA box and the presence of the Integrator complex rather than the Mediator complex (reviewed in Egloff et al. 2008, Jawdeker and Henry 2008).
The snRNA genes are among the most rapidly transcribed genes in the genome. The 5' transcribed region of the U2 snRNA gene is largely single-stranded during interphase and metaphase (Pavelitz et al. 2008) and chromatin within the transcribed region is cleared of nucleosomes (O'Reilly et al. 2014). Transcriptional activation of the RNA polymerase II transcribed snRNA genes begins with binding of transcription factors to the distal sequence element (DSE) of the promoter (reviewed in Hernandez 2001, Egloff et al. 2008, Jawdeker and Henry 2008). The factors, which include POU2F1 (Oct-1), POU2F2 (Oct-2), ZNF143 (Staf) and Sp1, promote binding of the SNAPc complex (also known as PTF and PBP) to the PSE. SNAPc helps clear the gene of nucleosomes (O'Reilly et al. 2014) and recruits initiation factors (TFIIA, TFIIB, TFIIE, TFIIF, and snTAFc:TBP) which recruit RNA polymerase II. Phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (reviewed in Egloff and Murphy 2008) by CDK7 recruits RPAP2 and the Integrator complex, which is required for later processing of the 3' end of the pre-snRNA transcript (reviewed in Chen and Wagner 2010, Baillat and Wagner 2015). The Little Elongation Complex (LEC) also appears to bind around the time of transcription initiation (Hu et al. 2013). As transcription proceeds, RPAP2 dephosphorylates serine-5 and P-TEFb phosphorylates serine-2 of the CTD. As transcription reaches the end of the snRNA gene serine-7 of the CTD is phosphorylated. These marks serve to bind protein complexes and are required for 3' processing of the pre-snRNA (reviewed in Egloff and Murphy 2008). After transcription proceeds through the conserved 3' processing sequence of the pre-snRNA the Integrator complex cleaves the pre-snRNA. Transcription then terminates downstream in a less well characterized reaction that requires elements of the polyadenylation system.

Literature References

PubMed ID	Title	Journal	Year
20659008	snRNA 3' end formation: the dawn of the Integrator complex Chen, J, Wagner, EJ	Biochem. Soc. Trans.	2010
18482001	Role of the C-terminal domain of RNA polymerase II in expression of small nuclear RNA genes Egloff, S, Murphy, S	Biochem. Soc. Trans.	2008
25882383	Integrator: surprisingly diverse functions in gene expression Baillat, D, Wagner, EJ	Trends Biochem. Sci.	2015
3837185	Human U1 small nuclear RNA genes: extensive conservation of flanking sequences suggests cycles of gene amplification and transposition Bernstein, LB, Manser, T, Weiner, AM	Mol. Cell. Biol.	1985
18442490	Transcriptional regulation of human small nuclear RNA genes Jawdekar, GW, Henry, RW	Biochim. Biophys. Acta	2008
11390411	Small nuclear RNA genes: a model system to study fundamental mechanisms of transcription Hernandez, N	J. Biol. Chem.	2001
22622228	Updating the RNA polymerase CTD code: adding gene-specific layers Egloff, S, Dienstbier, M, Murphy, S	Trends Genet.	2012
6201719	Human genes for U2 small nuclear RNA are tandemly repeated Van Arsdell, SW, Weiner, AM	Mol. Cell. Biol.	1984
18631122	Expression of human snRNA genes from beginning to end Egloff, S, O'Reilly, D, Murphy, S	Biochem. Soc. Trans.	2008
23932780	The little elongation complex functions at initiation and elongation phases of snRNA gene transcription Hu, D, Smith, ER, Garruss, AS, Mohaghegh, N, Varberg, JM, Lin, C, Jackson, J, Gao, X, Saraf, A, Florens, LA, Washburn, MP, Eissenberg, JC, Shilatifard, A	Mol. Cell	2013
24097444	Human snRNA genes use polyadenylation factors to promote efficient transcription termination O'Reilly, D, Kuznetsova, OV, Laitem, C, Zaborowska, J, Dienstbier, M, Murphy, S	Nucleic Acids Res.	2014
18378697	Human U2 snRNA genes exhibit a persistently open transcriptional state and promoter disassembly at metaphase Pavelitz, T, Bailey, AD, Elco, CP, Weiner, AM	Mol. Cell. Biol.	2008