When touring an unfamiliar city or museum, it often helps to have a good guide if you want to see the best sights. Researchers in Spain now report that intronic RNAs, like a well trained herding dog, usher the repressive polycomb complex right to the specific chromatin regions they need to target in order to repress epigenetic genes in a human cancer cell line.
Recent studies suggested that noncoding RNAs might have something to do with targeting the polycomb complex PRC2 to certain sites in the genome. So, the researchers used in vivo cross-linking and immunoprecipitation method called CLIP to find out which RNAs in a human colorectal cancer cell line bind to EZH2, which is a subunit of PRC2 that trimethylates H3K27 (H3K27me3 is repressive mark). Here’s what they discovered:
- Intronic RNA sequences bound specifically to EZH2.
- EZH2 binds to chromatin in the same places it binds to the RNAs, so the RNAs may have a regulatory effect in cis.
- Overexpressing the intronic RNA region near one of the EZH2 target genes (SMYD3; an H3K4 methyltransferase) represses its genomic counterpart, so the researchers say that the intronic RNA can work in trans.
- Overexpression of the intronic RNA also means more repression and more EZH2 bound on the genome.
- Research shows that SMYD3 may be involved in cancer. Mice transfected with colorectal cancer cells containing the SMYD3 intronic RNA had smaller tumors than those transfected with control colorectal cancer cells. So, the intronic RNA most likely downregulated SMYD3 to reduce tumor growth.
The team says all this evidence suggests that intronic RNAs can act kind of like transcription factors, guiding the polycomb complex to chromatin to fine-tune gene expression.
Let the paper be your guide at Nature Structural & Molecular Biology, June 2012.