piRNAs

piRNAs

Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi proteins. These piRNA complexes are mostly involved in the epigenetic and post-transcriptional silencing of transposons, but can also be involved in the regulation of other genetic elements in germ line cells. piRNAs are mostly created from loci that function as transposon traps and provide an RNA-mediated adaptive immunity against transposon expansions and invasions. They are distinct from microRNA (miRNA) in size (26–31 nt rather than 21–24 nt), lack of sequence conservation, and increased complexity.

Shielding the brain from jumping genes- 2019

Autopsies of people who died with Alzheimer’s disease show a buildup of a protein called tau in the brain. That tau accumulation is tied to loss of some guardian RNAs, according to work by Bess Frost, a neurobiologist at UT Health San Antonio.

Frost studies fruit flies genetically engineered to make a disease-causing version of human tau in their nerve cells. Flies with the disorderly tau get a progressive nerve disease that causes movement problems and kills nerves. The insects live shorter lives than normal.

Part of the reason the flies, as well as people with tau tangles, have problems is because some RNAs known to guard the genome fall down on the job, Frost and colleagues discovered. These piwi-interacting RNAs, or piRNAs (pronounced “pie RNAs”), help keep transposons from jumping around. When transposons jump, they may land in or near a gene and mess with its activity.

Usually cells prevent jumping by stopping transposons from making messenger RNA, which carries instructions to make proteins that eventually enable the transposon to hop from place to place. If a transposon gets past the cell’s defenses and produces its messenger RNA, piRNAs will step up to pair with the messenger and cause its destruction.

When disease-causing tau builds up in flies (and maybe in people), a class of transposon with a lengthy name — class I long terminal repeat retrotransposons — makes much more RNA than usual. And when flies have the disease-causing version of tau, they also have lower than normal levels of piRNAs, Frost and colleagues reported in August 2018 in Nature Neuroscience. “Both arms of control are messed up,” Frost says. Brains of people who died with Alzheimer’s disease or supranuclear palsy, another tau-related disease, also show signs that transposons were making extra RNA, suggesting that when tau goes bad, it can beat piRNA’s defenses.

In search of a work-around, Frost’s team found that genetically boosting piRNA production in flies or giving a drug that stops transposon hops reduced nerve cell death in the insects. The researchers are preparing to test the drug in mice prone to a rodent version of Alzheimer’s disease. The team is also examining human brain tissue to see if the increase in transposon RNAs actually leads to transposon jumping in Alzheimer’s patients. If transposons don’t hop more than usual, the finding may suggest that transposon RNAs themselves can cause mischief — no jumping necessary.

piRNAs

Attachments