Chimeras taking shape: Potential functions of proteins encoded by chimeric RNA transcripts
- Milana Frenkel-Morgenstern1,
- Vincent Lacroix2,
- Iakes Ezkurdia1,
- Yishai Levin3,
- Alexandra Gabashvili3,
- Jaime Prilusky3,
- Angela del Pozo4,
- Michael L Tress4,
- Rory Johnson5,
- Roderic Guigo5 and
- Alfonso Valencia6,7
- 1 Spanish National Cancer Research Centre (CNIO);
- 2 Universite Claude Bernard;
- 3 Weizmann Institute of Science;
- 4 Spanish National Cancer Research Centre;
- 5 Centre for Genomic Regulation (CRG);
- 6 Spanish National Cancer Research Centre- CNIO
- ↵* Corresponding author; email: avalencia{at}cnio.es
Abstract
Chimeric RNAs comprise exons from two or more different genes and have the potential to encode novel proteins that alter cellular phenotypes. To date, numerous putative chimeric transcripts have been identified among the ESTs isolated from several organisms and using high throughput RNA sequencing. The few corresponding protein products that have been characterized mostly result from chromosomal translocations and are associated with cancer. Here, we systematically establish that some of the putative chimeric transcripts are genuinely expressed in human cells. Using high throughput RNA sequencing, mass spectrometry experimental data and functional annotation, we studied 7,424 putative human chimeric RNAs. We confirmed the expression of 175 chimeric RNAs in 16 human tissues, with an abundance varying from 0.06 to 17 RPKM. We show that these chimeric RNAs are significantly more tissue-specific than non-chimeric transcripts. Moreover, we present evidence that chimeras tend to incorporate highly expressed genes. Despite the low expression level of most chimeric RNAs, we show that 12 novel chimeras are translated into proteins detectable in multiple shotgun mass spectrometry experiments. Furthermore, we confirmed the expression of three novel chimeric proteins using targeted mass-spectrometry. Finally, based on our functional annotation of exon organization and preserved domains, we discuss the potential features of chimeric proteins with illustrative examples and suggest that chimeras significantly exploit signal peptides and transmembrane domains, which can alter the cellular localization of cognate proteins. Taken together, these findings establish that some chimeric RNAs are translated into potentially functional proteins in humans.
- Received August 1, 2011.
- Accepted April 30, 2012.
- © 2012, Published by Cold Spring Harbor Laboratory Press
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