"We were surprised to find that lincRNA-p21 appears to be functioning as a global repressor, regulating hundreds of genes in the p53 pathway," said Maite Huarte, PhD, first and co-corresponding author."This lincRNA is playing defense for p53 to block other pathways in their efforts to interfere with p53's critical job of tumor suppression by cell death."

lincRNA-p21 carries out this function by roping in other critical factors in the cell nucleus to assist in tamping down expression at specific genes. "In the same way that air traffic controllers organize planes in the air, lincRNAs organize key nuclear complexes in the cell," said Rinn. "lincRNA-p21 specifically binds to a protein called hnRNP-K and then guides hnRNP-K to its final destination to shut down any genes that interfere with p53."

As exciting as these findings are for understanding multiple forms of cancer, they have far broader implications for understanding basic genome biology and multiple diseases. "We know that so-called 'transcription factors' can turn genes on by recruiting transcriptional machinery, but it has been less clear how they turn genes off," says Rinn. "lincRNAs could be those elusive 'anti-factors' that serve to shut genes down by reshuffling proteins around the genome."

Source: Beth Israel Deaconess Medical Center