Dataset Information

Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs.

ABSTRACT:

Background

Recent reports have highlighted instances of mRNAs that, in addition to coding for protein, regulate the abundance of related transcripts by altering microRNA availability. These two mRNA roles - one mediated by RNA and the other by protein - are inter-dependent and hence cannot easily be separated. Whether the RNA-mediated role of transcripts is important, per se, or whether it is a relatively innocuous consequence of competition by different transcripts for microRNA binding remains unknown.

Results

Here we took advantage of 48 loci that encoded proteins in the earliest eutherian ancestor, but whose protein-coding capability has since been lost specifically during rodent evolution. Sixty-five percent of such loci, which we term 'unitary pseudogenes', have retained their expression in mouse and their transcripts exhibit conserved tissue expression profiles. The maintenance of these unitary pseudogenes' spatial expression profiles is associated with conservation of their microRNA response elements and these appear to preserve the post-transcriptional roles of their protein-coding ancestor. We used mouse Pbcas4, an exemplar of these transcribed unitary pseudogenes, to experimentally test our genome-wide predictions. We demonstrate that the role of Pbcas4 as a competitive endogenous RNA has been conserved and has outlived its ancestral gene's loss of protein-coding potential.

Conclusions

These results show that post-transcriptional regulation by bifunctional mRNAs can persist over long evolutionary time periods even after their protein coding ability has been lost.

SUBMITTER: Marques AC

PROVIDER: S-EPMC3580494 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Publications

Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs.

Marques Ana C AC Tan Jennifer J Lee Sheena S Kong Lesheng L Heger Andreas A Ponting Chris P CP

Genome biology 20121115 11

<h4>Background</h4>Recent reports have highlighted instances of mRNAs that, in addition to coding for protein, regulate the abundance of related transcripts by altering microRNA availability. These two mRNA roles - one mediated by RNA and the other by protein - are inter-dependent and hence cannot easily be separated. Whether the RNA-mediated role of transcripts is important, per se, or whether it is a relatively innocuous consequence of competition by different transcripts for microRNA binding ...[more]

PMID: 23153069

Similar Datasets

Project description:BackgroundTranscribed pseudogenes are copies of protein-coding genes that have accumulated indicators of coding-sequence decay (such as frameshifts and premature stop codons), but nonetheless remain transcribed. Recent experimental evidence indicates that transcribed pseudogenes may regulate the expression of homologous genes, through antisense interference, or generation of small interfering RNAs (siRNAs). Here, we assessed the genomic evidence for such transcribed pseudogenes of potential functional importance, in the human genome. The most obvious indicators of such functional importance are significant evidence of conservation and selection pressure.ResultsA variety of pseudogene annotations from multiple sources were pooled and filtered to obtain a subset of sequences that have significant mid-sequence disablements (frameshifts and premature stop codons), and that have clear evidence of full-length mRNA transcription. We found 1750 such transcribed pseudogene annotations (TPAs) in the human genome (corresponding to approximately 11.5% of human pseudogene annotations). We checked for syntenic conservation of TPAs in other mammals (rhesus monkey, mouse, rat, dog and cow). About half of the human TPAs are conserved in rhesus monkey, but strikingly, very few in mouse (approximately 3%). The TPAs conserved in rhesus monkey show evidence of selection pressure (relative to surrounding intergenic DNA) on: (i) their GC content, and (ii) their rate of nucleotide substitution. This is in spite of distributions of Ka/Ks (ratios of non-synonymous to synonymous substitution rates), congruent with a lack of protein-coding ability. Furthermore, we have identified 68 human TPAs that are syntenically conserved in at least two other mammals. Interestingly, we observe three TPA sequences conserved in dog that have intermediate character (i.e., evidence of both protein-coding ability and pseudogenicity), and discuss the implications of this.ConclusionThrough evolutionary analysis, we have identified candidate sequences for functional human transcribed pseudogenes, and have pinpointed 68 strong candidates for further investigation as potentially functional transcribed pseudogenes across multiple mammal species.

Dataset Information

Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs.

Background

Results

Conclusions

Publications

Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs.

Similar Datasets

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