Enrique M. Muro Home Page
Enrique M. Muro, PhD.
E-mail: enrique.muro@mdc-berlin.de
Publications
Last News
Functional evidence of postranscriptional regulation by pseudogenes. Invited Review (accepted for publication)
Enrique M. Muro, Nancy Mah and Miguel A. Andrade
Natural Antisense Transcripts within Pseudogenes: an EST Survey. From the book Non-coding RNAs and Epigenetic Regulation of Gene Expression: Drivers of Natural Selection(edited by Kevin V. Morris)
Enrique M. Muro and Miguel A. Andrade
Pseudogenes are genome loci that look like genes but have sequences apparently prevented to produce any functional product due to genetic defects. However, recent advances in the field of molecular biology urge the revisiting of this definition. In this chapter we will discuss some of those advances. There is experimental and computational evidence of some biological function arising from pseudogene transcription but this evidence is not easy to find. Accordingly, not that many studies have been published on the topic. It seems that if there is pseudogene transcript functionality, it arises in certain tissues, and in certain conditions, with much more specificity than gene expression. Some of this complexity relates to the fact that this function involves non-coding RNAs (ncRNAs), a molecular entity for which novel tools and biological paradigms are still being worked out. A particular type of ncRNAs are Natural Antisense Transcripts (NATs) and these have a special relevance for the study of pseudogene functionality for reasons that we will discuss.
The pseudogenes of Mycobacterium leprae reveal the functional relevance of gene order within operons.
Muro EM, Mah N, Moreno-Hagelsieb G, Andrade-Navarro MA. Nucleic Acids Res. 2010 Nov 4.ABSTRACT:
BACKGROUND: Naturally occurring antisense transcripts (NATs) are non-coding RNAs that may regulate the activity of sense transcripts to which they bind because of complementarity. NATs that are not located in the gene they regulate (trans-NATs) have better chances to evolve than cis-NATs, which is evident when the sense strand of the cis-NAT is part of a protein coding gene. However, the generation of a trans-NAT requires the formation of a relatively large region of complementarity to the gene it regulates.
RESULTS: Pseudogene formation may be one evolutionary mechanism that generates trans-NATs to the parental gene. For example, this could occur if the parental gene is regulated by a cis-NAT that is copied as a trans-NAT in the pseudogene. To support this we identified human pseudogenes with a trans-NAT to the parental gene in their antisense strand by analysis of the database of expressed sequence tags (ESTs). We found that the mutations that appeared in these trans-NATs after the pseudogene formation do not show the flat distribution that would be expected in a non functional transcript. Instead, we found higher similarity to the parental gene in a region nearby the 3' end of the trans-NATs.
CONCLUSIONS: Our results do not imply a functional relation of the trans-NAT arising from pseudogenes over their respective parental genes but add evidence for it and stress the importance of duplication mechanisms of genetic material in the generation of non-coding RNAs. We also provide a plausible explanation for the large transcripts that can be found in the antisense strand of some pseudogenes.
Pseudogenes as an alternative source of natural antisense transcripts.
Muro EM, Andrade-Navarro MA. BMC Evol Biol. 2010 Nov 3;10(1):338. ABSTRACT:BACKGROUND: Naturally occurring antisense transcripts (NATs) are non-coding RNAs that may regulate the activity of sense transcripts to which they bind because of complementarity. NATs that are not located in the gene they regulate (trans-NATs) have better chances to evolve than cis-NATs, which is evident when the sense strand of the cis-NAT is part of a protein coding gene. However, the generation of a trans-NAT requires the formation of a relatively large region of complementarity to the gene it regulates.
RESULTS: Pseudogene formation may be one evolutionary mechanism that generates trans-NATs to the parental gene. For example, this could occur if the parental gene is regulated by a cis-NAT that is copied as a trans-NAT in the pseudogene. To support this we identified human pseudogenes with a trans-NAT to the parental gene in their antisense strand by analysis of the database of expressed sequence tags (ESTs). We found that the mutations that appeared in these trans-NATs after the pseudogene formation do not show the flat distribution that would be expected in a non functional transcript. Instead, we found higher similarity to the parental gene in a region nearby the 3' end of the trans-NATs.
CONCLUSIONS: Our results do not imply a functional relation of the trans-NAT arising from pseudogenes over their respective parental genes but add evidence for it and stress the importance of duplication mechanisms of genetic material in the generation of non-coding RNAs. We also provide a plausible explanation for the large transcripts that can be found in the antisense strand of some pseudogenes.
Web Servers
We observed that the databases of expressed sequence tags (ESTs) contain abundant evidence pointing to alternative 3'UTR ends currently absent of the databases for many genes, and invalidating many of the database transcript ends. We propose and verify a method to predict transcript ends using EST data and analysis of poly-adenylation signals. The results of the analysis of the complete human and murine genomes are available as data tables and through the Transcriptome Sailor web tool, which allows examination of particular genomic regions for predictions and evidence.
Muro, E.M., R. Herrington, S. Janmohamed, C. Frelin, M.A. Andrade-Navarro, and N.N. Iscove. 2008. Identification of gene 3′ ends by automated EST cluster analysis. Proc. Natl. Acad. Sci. 150, 20286-20290. [Transcriptome Sailor]
Probe2GO is a server that distributes Gene Ontology annotations that we predict for Affymetrix DNA microarray probe sets using data deposited in a number of databases.
The predicted annotations and the evidence leading to them can be accessed by probe set identifier, but it is also possible to link directly to the evidence.
Amplification of the Gene Ontology annotation of Affymetrix probe sets. Enrique M. Muro, Carolina Perez-Iratxeta, Miguel A. Andrade-Navarro BMC Bioinformatics 2006, 7:159 (20 March 2006)
