New research is advancing understanding of the function of non-coding regions of the human genome.
Writing in Nature Genetics last week, researchers report findings from an analysis where they mapped the known exons (protein coding regions within genes) of the genome and their potential folding and resulting topography. They found evidence that the genomic structure locates some exons close to transcriptional elements, making them more accessible for transcription and RNA splicing.
The researchers propose that the genome can form protected pockets where transcription and rapid splicing of exons can take place in effective isolation from other genomic regions, and this compartmentalisation helps to ‘generate the complex, interleaved networks of transcripts that are a feature of the human genome’ by creating an additional mechanism for alternative splicing, the process by which RNA sequences copied from a given gene are edited to specify the production of different proteins.
The research used data generated by ENCODE, an international project investigating the functional elements of the human genome. Dr Tim Mercer said: "This study provides the first indication that the three-dimensional structure of the genome can influence the splicing of genes".
A separate study published in PLOS Genetics reports the discovery of a large new set of RNA sequences produced by transcription of the majority of the human genome sequence that does not code for the production of proteins. Around 85% of this non-coding DNA was found to be copied into a type of RNA molecules dubbed Long Intergenic Noncoding RNAs or lincRNAs. Previous research has shown that lincRNAs can have functions in controlling gene expression; the researchers conclude that the expanded set of lincRNAs ‘will enable the discovery and interrogation of novel intergenic functional elements’.
Comment: When the human genome project began, it was genuinely believed that determining the genome sequence would effectively map the acclaimed ‘blueprint of life’. In fact this historic achievement, though representing a huge scientific leap forwards, was only the start of the quest to understand how the human genome functions in health and disease. Already, the original belief that most of the genome sequence (the non-coding regions) was simply redundant or ‘junk’ DNA seems almost ridiculous as evidence of the intricate and strangely compelling complexity of gene expression continues to emerge. However, further revelations are to be expected, driven by the power of international collaborations, massive data sets, and ever more sophisticated analytical techniques.