Yet Another Class of RNA Discovered

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Published online: 4 June 2006; | doi:10.1038/news060529-12

Mice testicles reveal new class of RNAs

Mini cousins of DNA could play vital role in sperm formation.

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A whole new type of RNA has been discovered.

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

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.