( r stop sign telling another protein ca...)From a Lowly Yeast, Researchers Divine a Clue to Human Disease,Health

r stop sign, telling another protein called RNA polymerase II when to stop transcribing genetic information from DNA into related threads of RNA. The polymerase reads along DNA strands, building RNA as it goes. Multiple genes strung along a single length of DNA are separated by gaps to mark boundaries. As the polymerase reaches the end of a gene, Sen1 flips a switch and knocks it off the DNA track.

The group, led by Brow and Eric Steinmetz, compared normal yeast to a strain with a mutated form of Sen1 that does not see the stop signal. "The Sen1 mutant reads right through the stop sign and keeps going," Brow says.

Without a properly functional Sen1, RNA polymerase II "reads through" the end of the gene and builds longer and longer RNA messages. "In some cases it doesn't have a big effect," Brow says. "Other times, it's a big problem," like when another important gene is right next-door on the same piece of DNA.

Like run-on sentences, long RNAs from multiple genes are confusing and hard or impossible for the cell to use. "It really messes up a lot of things, not just the read-through gene but also adjacent genes," Brow says.

In other cases, Sen1 stop signs near the beginning of some genes normally prevent RNA polymerase II from making RNA from those genes. Sen1 mutations, on the other hand, allow access to these messages, triggering genes that normally aren't operational.

These garbled genetic messages -- whether with too much or too little genetic information -- can disrupt the normal functions of cells and, in some cases, lead to disease. Sen1 mutations are likely to have similar effects in humans, says Brow. By adapting his approach, other researchers may be able to identify specific genes affected in the human Sen1-linked neurological disorders.

Source-Newswise
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