The upSET over non-coding RNAs: how chromatin structure governs their production

Posted by Biome on 14th June 2013 - 0 Comments

The more we learn about the expression of eukaryotic genomes, the clearer it becomes that this process is more complex than previously believed. The rather simplistic idea that transcription is restricted solely to protein-coding genes or those encoding non-coding RNAs (ncRNAs) that regulate translation (such as rRNAs and tRNAs) has long been overturned. In a review published in Epigenetics & Chromatin, Jerry Workman and colleagues at the Stowers Institute for Medical Research, USA, discuss the more complicated story that has since evolved; specifically focusing on mechanisms that regulate the transcription of other ncRNAs. The authors distil recent findings on how chromatin structure affects the production of these ncRNAs. This detailed review is part of the thematic series, ‘Epigenetics & Chromatin: Interactions and processes‘, which marks the launch of the 2013 BioMed Central conference of the same name.

The extent to which the genome is transcribed has been shown to be greater than initial estimates, notably up to 85 percent of the yeast genome is suggested to be transcribed and 75 percent of the human genome. It is now believed that conventional 5’ to 3’ transcription of protein-coding genes is not the only contributor to the transcriptome. Workman and colleagues begin by highlighting how transcription can be initiated from multiple transcription start sites (leading to overlapping transcripts) or even from the ends of genes (resulting in antisense or intergenic transcripts). Although this may sound rather chaotic, transcription of ncRNAs is actually tightly controlled. The regulation of nucleosome positions and chromatin structure is key to this control, as the authors go on to discuss.

The solution structure of the SRI domain of yeast Set2 that binds to RNA polymerase II during transcription. Image source: RSCB PDB, file 2C5Z

The highly organised structure of chromatin prevents the spurious production of excessive amounts of ncRNAs. In this review the authors provide an overview of the different strategies used to maintain chromatin integrity, focusing in particular on the RNA polymerase II-associated lysine methyltransferases, Set1 and Set2, which have key roles in this process. Inactivation of Set2, for example, results in the activation of cryptic promoters, which are normally suppressed, leading to the generation of ncRNAs. Workman and colleagues focus on studies in yeast, however the mechanisms explored are also expected to apply to higher eukaryotes.

The authors conclude with a brief discussion of the role of ncRNAs. Given that their production is highly regulated, it is thought that some of them at least (such as PHO84 and SRG1-SER3 in yeast) may function as regulatory molecules under certain growth conditions. A conclusive answer to the question of what ncRNAs do requires much further investigation, however this review offers a detailed look at how these ncRNAs come about in the first place.



UpSETing chromatin during non-coding RNA production

Venkatesh S, Workman JL and Smolle M
Epigenetics & Chromatin 2013, 6:16

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