SINE RNAs

SINEs or Short Interspersed Nuclear Elements are sequences of non-coding DNA present at high frequencies in various eukaryotic genomes. They are a class of retrotransposons, DNA elements that amplify themselves throughout eukaryotic genomes, often through RNA intermediates. Short-interspersed nuclear elements are characterized by their size and method of retrotransposition.  Non-LTR retrotransposons consist of two sub-types, long interspersed elements (LINEs) and short interspersed elements (SINEs).

Short-interspersed nuclear elements are believed to have parasitic origins in eukaryotic genomes. These SINEs have mutated and replicated themselves an incredible amount of times on an evolutionary time-scale and thus form many different lineages. Their early evolutionary origin has caused them to be ubiquitous in many eukaryotic lineages. In fact, the Alu element, a short-interspersed nuclear element of about 300 nucleotides is located at over a million copies throughout the human genome, which is over 10 percent of the total genome; this is not uncommon among other species.[8] The Alu family of sines are among an incredible amount of eukaryotic SINEs distinguished by different features including their length, sequence, and method of retrotransposition.

One class of transposons, called SINEs for short interspersed nuclear elements, are peppered throughout the genome. People have more than a million of one type of SINE known as Alu elements. Mice have similar SINEs, called B2s.

When active, SINE transposons make RNA copies of themselves. These SINE RNAs don’t carry instructions for building proteins and alone don’t enable the transposons to jump around the genome. So researchers puzzled over their role. Glaunsinger and colleagues discovered that some SINE RNAs may protect against viral infections.

Another type of RNA may help protect against infection by certain viruses, including herpesvirus. Virologist Britt Glaunsinger has long marveled at the way viruses manipulate host cells by controlling RNAs in the cell. She became intrigued by transposons, mobile stretches of DNA that can jump from one location to another in the genome. Transposons make up nearly half of all the DNA in the human genome (SN: 5/27/17, p. 22). “We tend to think of [transposons] as parasites and things our own cells are constantly trying to shut down,” says Glaunsinger, a Howard Hughes Medical Institute investigator at the University of California, Berkeley. That’s because some are relics of ancient viruses. “While they may have initially been bad, some of them may actually be useful to us,” she says.

Normally, cells keep a tight lock on transposons, preventing them from making any RNA. But in Glaunsinger’s experiments, cells infected with herpesvirus “were producing tons of these noncoding RNAs in response to infection,” she says. “That sort of captured our interest.” 

Details of the process are still being worked out, but Glaunsinger and others have discovered that SINE RNA production triggers a cascade of events that eventually kills infected human and mouse cells. Once the RNA production gets going, Glaunsinger says, “the cell is destined to die.” Inflammation appears to be an important step in the cell-killing chain reaction. It’s all for the greater good: Killing the infected cell may protect the rest of the organism from the infection’s spread. 

But there’s a wrinkle: In mice, at least, one type of herpesvirus benefits from the flood of B2 RNAs in the cells it infects. The virus hijacks part of the inflammation chain reaction to boost its own production, Glaunsinger and colleagues reported in 2015 in PLOS Pathogens. “This is an example of the back-and-forth battle that’s always going on between virus and host,” she says. “Now the ball is back in the host’s court.”

SINE RNAs

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