Intron retention enhances gene regulatory complexity in vertebrates
- Authors
- Schmitz, U., Pinello, N., Jia, F., Alasmari, S., Ritchie, W., Keightley, M.C., Shini, S., Lieschke, G., Wong, J., Rasko, J.
- ID
- ZDB-PUB-180515-15
- Date
- 2017
- Source
- Genome biology 18: 216 (Journal)
- Registered Authors
- Alasmari, Sultan, Keightley, M. Cristina, Lieschke, Graham J.
- Keywords
- Transcriptomic complexity, Granulocytes, Evolution, Alternative splicing, Intron retention, Gene regulation
- MeSH Terms
-
- Animals
- Binding Sites/genetics
- Conserved Sequence/genetics
- Gene Expression Regulation*
- Genome
- Humans
- Introns/genetics*
- Male
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Promoter Regions, Genetic/genetics
- Species Specificity
- Time Factors
- Vertebrates/genetics*
- PubMed
- 29141666 Full text @ Genome Biol.
While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution.
Results
Our RNA-sequencing-based analysis suggests that IR increases gene regulatory complexity, which is indicated by a strong anti-correlation between the number of genes affected by IR and the number of protein-coding genes in the genome of individual species. Our results confirm that IR affects many orthologous or functionally related genes in granulocytes. Further analysis uncovers new and unanticipated conserved characteristics of intron-retaining transcripts. We find that intron-retaining genes are transcriptionally co-regulated from bidirectional promoters. Intron-retaining genes have significantly longer 3′ UTR sequences, with a corresponding increase in microRNA binding sites, some of which include highly conserved sequence motifs. This suggests that intron-retaining genes are highly regulated post-transcriptionally.
Conclusions
Our study provides unique insights concerning the role of IR as a robust and evolutionarily conserved mechanism of gene expression regulation. Our findings enhance our understanding of gene regulatory complexity by adding another contributor to evolutionary adaptation.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-017-1339-3) contains supplementary material, which is available to authorized users.