ReseaRch highlights

TRANSCRIPTOmICS There’s nothing abnormal about chimeric RNA

Chimeric RNAs and the proteins present in various normal endome- were found containing rhesus and translated from them often have trial cell lines. Using RT-PCR, human sequences, showing that the a causal role in tumorigenesis. RNase protection and western blot- mRNAs had been spliced together They are also occasionally found ting they showed that the chimeric rather than arising either from at low levels in healthy cells. These JAZF1–JJAZ1 mRNA and protein rearrangements in DNA or from phenomena were previously thought are found — with identical sequence the polymerase switching templates to be the result exclusively of DNA to that in cancer cells — in endome- during . rearrangements, but a new study trial cells but not in other cell types. The next step will be to discover shows that trans-splicing of mRNAs The levels of the chimeric the mechanism by which two can be a frequent and regulated mRNA oscillated with the men- separate mRNAs are selected for occurrence in some normal cells. strual cycle in a predictable fashion, splicing together. It is intriguing that A chromosomal translocation implying that the process is regu- gene fusions in cancer cells have that joins the first 3 of JAZF1 lated rather than accidental. The recapitulated the normal synthesis to the last 15 exons of JJAZ1 (also authors investigated this further of chimeric products that in normal called SUZ12) has been found in by showing that steroid hormones cells is mediated at the mRNA level. several endometrial cancers, and has and hypoxia could alter levels of It will be interesting to see whether been shown to confer resistance to the chimeric mRNA, and that co-localization of the genes during apoptosis when expressed in normal these treatments did not affect the transcription, which is possibly cells. Sklar and colleagues investi- expression of the separate JAZF1 required for trans-splicing to occur, gated whether a similar fusion is and JJAZ1 mRNAs. predisposes towards the gene fusion So, are chromosomal fusions or whether it is merely that the responsible for these chimeric growth advantages of this fusion are mRNAs? Southern blotting and selected for when, by chance, they fluorescence in situ hybridization occur in cancer cells.

PHOTOALTO (FISH) showed no evidence of Patrick Goymer any gene fusion at the DNA level,

leading the authors to investigate ORIGINAL RESEARCH PAPER Li, H., Wang, J., trans-splicing of the individual Mor, G. & Sklar, J. A neoplastic gene fusion mimics mRNAs. When an extract from trans-splicing of RNAs in normal human cells. Science 321, 1357–1361 (2008) endometrial cells that can medi- FURTHER READING Kapranov, P., Willingham A. ate splicing in vitro was mixed T. & Gingeras, T. R. Genome-wide transcription and the implications for genomic organization. with purified RNA from rhesus Nature Rev. Genet. 8, 413–423 (2007) fibroblast cells, chimeric products

NATURe RevIeWS | geNeTics volUme 9 | oCTobeR 2008