"It is the timing and duration of expression of the set of p53 target genes that are turned on, which strongly influences cell fate decisions," says Jones, who likes to compare PUMA, which takes its time to come online, and p21Cip1, which quickly snaps into action in response to damage, to Aesop's fable of the tortoise and the hare. "Cell cycle arrest genes are poised for immediate action, whereas pro-apoptotic genes go slow but steady."
Even before cell damage occurs, these genes differ in the number and composition of their pre-loaded transcription complexes. These multi-protein assemblies, called RNA polymerase II (Pol II), slide along the DNA's double helix, reading the genetic code and transcribing it into RNA, which is used as a blueprint to build proteins, or as a switch to regulate other genes. But Pol II is prone to stalling in the middle of transcribing genes and needs to be prodded along by elongation factors such as SKIP. "Under stressful conditions everything changes," explains Jones. "Elongation factors seem to be no longer necessary for transcription."
But SKIP influences gene expression in more than one way. It also plays an important role during the splicing process, which removes intervening sequences or introns, and joins the remaining pieces or exons to form a mature messenger RNA that can now be used to produce protein.
It is the splicing function that p21Cip1 cannot do without, revealed the experiments by postdoctoral researchers Yupeng Chen, Ph.D., and Lirong Zhang, Ph.D. "SKIP is critical for splicing and expression of p21Cip1, but not for PUMA or any of the other p53-induced gen
|Contact: Gina Kirchweger|