EpiGenie recently reviewed the epigenetic text Non-Coding RNAs and Epigenetic Regulation of Gene Expression by Kevin Morris. To give you a little taste of the material covered in the book, here is a summary of one of the chapters:
Natural Antisense Transcripts within Pseudogenes: An EST Survey
by Enrique M. Muro and Miguel A. Andrade-Navarro
Noncoding RNA (ncRNA) is increasingly gaining recognition as an important mechanism of gene regulation. This chapter focuses specifically on the potential origins of a class of ncRNA molecules that are Natural Antisense Transcripts (NATs) that may regulate protein-coding genes in trans, that is, at a different genomic locus. The authors present a hypothesis based on bioinformatic analyses of EST and pseudogene databases that such trans-acting NATs may arise from pseudogenes, primarily ones that are the result of gene duplication.
What are Pseudogenes?
Pseudogenes are genomic regions that resemble genes but are lacking critical elements, such as promoters and introns, which are necessary to render a functional protein product. In addition, pseudogenes may be distinguished from the “parent genes” they resemble by frameshift mutations or premature stop codons. Pseudogenes may arise through several distinct mechanisms. These include:
- Gene duplication followed by mutations that cause loss of function. These “non-processed” pseudogenes typically retain introns and other regulatory elements.
- Retrotransposition of the mRNA transcript of the parental gene into a separate genomic locus which may be on the same or different chromosome. These “processed” pseudogenes are intronless and resemble cDNA of the original transcript.
- Genetic disabling of a unique gene (e.g., by mutations, deletions or insertions) may also result in a pseudogene, with the complete loss of the original functional gene product that is no longer essential for the survival of the organism.
Natural Antisense Transcripts: Functions and Origins
NATs are identified by partial sequence complementarity to protein-coding transcripts, and are typically ncRNAs. These transcripts may regulate gene expression in a variety of ways, including RNA editing, splicing, and masking, as well as through epigenetic mechanisms. Estimates of genes with NATs range from 20-60%. Although cis-NATs are obviously derived from transcription of the antisense strand of the parent gene and necessarily co-evolve with the parent gene, the origin and evolution of trans-NATs is less clear.
In this chapter, the authors describe bioinformatic analyses that take into consideration transcript polyadenylation signals, combined with EST clustering, to identify NATs that are present in predicted pseudogenes. They found that pseudogenes are a rich source of trans-NATs that can regulate parent genes at a distance relative to the pseudogene location. Interestingly, in contrast to the low proportion (~10%) of duplicated pseudogenes predicted by genomic analyses, the large majority (90%) of the pseudogenes found to harbor trans-NATs arose by duplication of the parent genes along with their associated cis-NATs. The significance of these findings is that trans-NATs may evolve separately to aberrantly regulate the parent genes in different tissues or under a different set of conditions, such as those associated with various diseases.
**This chapter summary was provided by Valerie Hu, Ph.D. who is a Professor in the Department of Biochemistry and Molecular Biology at The George Washington University Medical Center.
You can get your own copy of Non-Coding RNAs and Epigenetic Regulation of Gene Expression at the Horizon Press website.