The Multifaceted Human Transcriptome

Abstract

A large amount of experimental data collected over the last decade has shown that genomic organization is very complex and has highlighted the fact that the current set of gene annotations does not fully capture this complexity. Furthermore, the transcriptome complexity has expanded in several directions. First, there is a significant amount of RNA that can be detected in a cell that originates from outside the exons of annotated genes, representing a multiplicity of novel exons of protein coding genes and stand alone transcripts. Second, exons of annotated and unannotated transcripts separated by large genomic distances can be joined together in chimeric transcripts. Third, individual compartments within the cell differ in the amount of un‐annotated transcription with nucleus and polyA‐ transcriptomes being highly enriched in un‐annotated transcripts. Fourth, the short RNA component of the transcriptome is vast and underappreciated. These results suggest that the functional space of the human genome is not limited to the annotated exons of protein coding genes and is likely to produce a vast amount of non‐coding RNAs. What are the implications of such genomic architecture in terms of increased information content, transcriptional complexity, evolution and disease states?