Mice testicles reveal new class of RNAs - RNAi

Mice testicles reveal new class of RNAs
4 June 2006;
Erica Cheek
newsatnature.com
Time to revise biology textbooks once again: scientists have discovered a new class of small RNAs lurking in mouse testicles.
The discovery is the latest to open up new frontiers in the study of small RNAs, a kind of genetic cousin to DNA. Discovered less than a decade ago, small RNAs are now known to regulate key processes in human health; RNA interference, for example, describes one important way that the body can shut off genes in invading pathogens.
The discovery of a new class of these genetic molecules is even more intriguing because it comes just after a report that RNA may transmit inherited information down through the generations (see 'Mutant mice challenge rules of genetic inheritance').
"It's almost like the beginning of the RNA interference field all over again ? now we have a whole other class of small RNAs and proteins to figure out," says Greg Hannon of Cold Spring Harbor Laboratory in New York.
Hannon's lab publishes one of two papers reporting the discovery today in Nature1. The other paper comes from the labs of Thomas Tuschl at the Rockefeller University in New York and Mihaela Zavolan at the University of Basel in Switzerland2.
Interfering proteins
Both Tuschl and Hannon found the new class of RNAs by cataloging the entire RNA content of mouse testicles. When they did this, they uncovered a glut of RNAs that were slightly longer than the varieties of small RNAs that have already been discovered ? such as microRNAs (mRNAs) and short interfering RNAs (siRNAs).
The researchers decided to check whether the new RNAs might be associated with a set of mysterious yet important proteins, called Piwi proteins. These proteins are expressed in the testes, and when they're shut off, mice can't make normal sperm. Piwis resemble other proteins that interact with small RNAs, but no one had yet identified an RNA partner for a Piwi protein.
Making an educated guess, the scientists pulled individual Piwi proteins out of mouse testes and checked what came along with them. Lo and behold, they found strands of the mysterious new RNAs stuck to the Piwi proteins.
They have named the new molecules "Piwi-interacting RNAs" ? piRNAs for short.
RNA intrigue
Now the race is on to try to figure out what, exactly, the piRNAs do.
Scientists only know a few things about them. The teams have sequenced the "letters" of these longer RNAs; like DNA, RNA is a string of chemical building blocks called nucleotides. They found that piRNAs have many different sequences, but they almost always start with one chemical letter: uridine.
Tuschl and Hannon found that they come from specific regions of chromosomes. They also know that similar types of RNAs exist in zebrafish and flies, and in human testes.
Given that mice need piRNAs and Piwi proteins to make sperm, scientists are now intrigued by the idea that piRNAs and Piwis might control some of the huge changes that give rise to sperm ? for example, the cell divisions that halve a cell's genetic material in the process of meiosis.

There is, as yet, no evidence for that, says Tuschl, who is reluctant to guess how the piRNAs work: "You can make really wild speculations, but I didn't make any of these in the paper because I'm afraid it's going to be too embarrassing later."
But what is clear, scientists say, is that the new discovery is yet another promising lead for the fast-moving RNA field. "The message for me is that every time we think we understand something about this process, we open a whole new door, and we see data that makes us view this in a whole new light," Hannon says.