User:ST WE/pRNA
Promoter associated RNAs (pRNAs) are a family of 90-100 nucleotides long RNAs located directly upstream of the rDNA promoter. pRNAs play an important role for rDNA methylation and silencing.
Formation and Function
[edit]The promoter-associated RNAs orginate from an intergenic spacer Pol I promoter located about 2 kb upstream of the pre-ribosomal RNA transcription start site [1]. Normally these intergenic transcripts are short-lived and degraded by the exosome. But there is one exception for a 150-250 nt transcript that matches the rDNA promoter and therefore termed promoter-associated RNA [2]. These pRNAs are stabilzed by binding to TIP 5 (TIF interacting protein 5), the large subunit of the chromatin remodeling complex NoRC, which mediates heterochromatin formation and transcriptional silencing [3]. This interaction is a prerequisite for the NoRC function, because antisense mediated depletion of pRNA leads to decreased rDNA methylation and activation of RNA polymerase I (Pol I) transcription [1]. The 5' terminal part of pRNA is believed to recruit DNMT3b to rDNA by forming a triple helical structure and directing therewith DNA methylation [4] [5].The release mechanism of the pRNA is regulated by the acetyltransferase MOF (males absent on the first), which acetylates a single lysine residue (K633) of TIP5 and leads to a dissociation of the pRNA from NoRC [6].
Secondary Structure
[edit]The pRNA secondary structure is predicted to form a hairpin, that is important for the function, because the hairpin is recognized by the TIP5 (TTF-I Interactiong Protein 5) and is a prerequisite of the guiding of the NoRC to the nucleolus [3]. If this secondary structure conserved among all Eutheria is doubtable.
Species distribution
[edit]Promoter associated RNAs are described in vitro in mouse and human. Furthermore they are predicted in all Eutheria by computational analyses.
References
[edit]- ^ a b Christine Mayer and Kerstin-Maike Schmitz and Junwei Li and Ingrid Grummt and Raffaella Santoro. Intergenic transcripts regulate the epigenetic state of rRNA genes. Molecular Cell. 2006;22:351--361. doi:10.1016/j.molcel.2006.03.028.
- ^ Santoro, R and Schmitz, K M and Sandoval, J and Grummt, I. Intergenic transcripts originating from a subclass of ribosomal DNA repeats silence ribosomal RNA genes in trans. EMBO Rep. 2010;11:52-58. doi:10.1038/embor.2009.254. PMID 20010804.
- ^ a b Christine Mayer and Melanie Neubert and Ingrid Grummt. The structure of NoRC-associated RNA is crucial for targeting the chromatin remodelling complex NoRC to the nucleolus. EMBO Reports. 2008;9:774-780. doi:10.1038/embor.2008.109.
- ^ Grummt, I. Wisely chosen paths--regulation of rRNA synthesis: delivered on 30 June 2010 at the 35th FEBS Congress in Gothenburg, Sweden. FEBS J. 2010;277:4626-4639. doi:10.1111/j.1742-4658.2010.07892.x. PMID 20977666.
- ^ Grummt, I and Längst, G. Epigenetic control of RNA polymerase I transcription in mammalian cells. Biochim Biophys Acta. 2013;(1829):393-404. doi:10.1016/j.bbagrm.2012.10.004. PMID 23063748.
- ^ Zhou, Y and Schmitz, K M and Mayer, C and Yuan, X and Akhtar, A and Grummt, I. Reversible acetylation of the chromatin remodelling complex NoRC is required for non-coding RNA-dependent silencing. Nat Cell Biol. 2009;11:1010-1016. doi:10.1038/ncb1914. PMID 19578370.