Pseudo-messenger RNA: phantoms of the transcriptome

Area of Science:

• Genomics
• Transcriptomics
• Bioinformatics

Background:

• Mammalian transcriptomes contain unclassified RNA molecules.
• Pseudo-messenger RNAs (pmRNAs) resemble mRNA but lack full protein-coding potential due to reading frame disruptions.

Purpose of the Study:

• To computationally identify and characterize pseudo-messenger RNAs (pmRNAs) within the FANTOM3 mouse cDNA dataset.
• To assess the prevalence and potential functions of these non-standard transcripts.

Main Methods:

• Development of a rigorous computational pipeline to identify pmRNAs, excluding sequencing errors.
• Analysis of 102,801 FANTOM3 mouse cDNAs to detect reading frame disruptions.

Main Results:

• Identified 10,679 pmRNAs, constituting over 10% of the FANTOM3 transcriptome.
• Approximately 50% of identified pmRNAs are associated with transposons.
• pmRNAs include transcribed pseudogenes and disrupted splice variants; some may encode truncated proteins.
• Evidence suggests a higher number of selenoproteins than currently estimated, indicated by opal stop codon disruptions.
• Observed compensatory frameshifts enabling translatability within disrupted segments.

Conclusions:

• Pseudo-messenger RNAs represent a significant, understudied class of transcripts in the mammalian transcriptome.
• These pmRNAs may possess novel biological functions and encode genetic information in non-standard ways.
• The existence of pmRNAs highlights limitations in fully annotating functional elements solely at the genome sequence level.