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'Dead' gene comes to life, puts chill on inflammation, Stanford researchers find
Date:7/23/2013

le genes, don't code for proteins. More than 11,000 pseudogenes one for every two protein-coding genes have been identified in the human genome. Scientists believe pseudogenes are copies of actual genes that, during the replication of some ancestral organism's germ cell, were accidentally inserted into the genome and, redundant but harmless, came along for the evolutionary ride. Over the intervening eons, these genetic doppelgangers have roamed along the genome, mutated and decayed to the point where, it is believed, they no longer do anything at all.

"Pseudogenes have been considered to be completely silent, ignored by cells' DNA-reading machinery," Chang said. "But we got a real surprise. When a cell is subjected to an inflammatory stress signal, it's like Night of the Living Dead."

Equally surprising, Chang said, is that different signaling chemicals or microbial components (such as bits of bacterial cell walls or of viral DNA) wake up different groups of lncRNA-encoding DNA sequences, including pseudogenes. "They're not really dead, after all. They just need very specific signals to set them in motion."

Lethe was one such pseudogene tripped off by stimulation of NF-kappa-B. Lethe directly interfered with the complex's ability to seat itself on appropriate DNA sequences, shutting down the pro-inflammatory genes the transcription factor ordinarily activates.

Several pseudogenes were activated in a selective manner. For example, TNF-alpha and another circulating signaling protein but not microbial parts activated Lethe.

Because some pseudogenes sit near protein-coding genes, some scientists have argued that the generation of RNA transcripts from the pseudogenes is simply an artifact of normal transcription of full-fledged protein-coding genes. "There's a tendency to assume it's some protein-coding gene that NF-kappa-B is really targeting, and to downplay the activation of a lncRNA as noise, a 'ripple effect' like the
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Contact: Bruce Goldman
goldmanb@stanford.edu
650-725-2106
Stanford University Medical Center
Source:Eurekalert

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