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
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. 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. 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. 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. The 5' terminal part of pRNA is believed to recruit DNMT3b to rDNA by forming a triple helical structure and directing therewith DNA methylation .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.

Secondary Structure
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. If this secondary structure conserved among all Eutheria is doubtable.

Species distribution
Promoter associated RNAs are described in vitro in mouse and human. Furthermore they are predicted in all Eutheria by computational analyses.