Undoing a hairpin doubles gene activity

Jul 29, 2013
Undoing a hairpin doubles gene activity
Genes on the single X chromosome in males (green) are twice as active as those on each of the two X chromosomes in females. The immunofluorescence image shows giant polytene chromosomes from the salivary glands of a male Drosophila larva, stained to reveal chromosomal DNA (blue) and a protein component of the dosage compensation complex on the X chromosome (green).

Male fruit flies have one X chromosome per cell, females have two. So genes on the male X must work twice as hard to produce the same amount of protein as its female counterparts. An LMU team has found a new switch involved in making this possible.

In the fruit fly Drosophila – as in humans – the sexes have different sets of . While females have two X chromosomes in their , males have one X and one copy of the much smaller Y. The latter determines maleness but carries very few , while the X chromosome has thousands of genes. Many of these encode essential proteins that must be made in equal amounts in both sexes, and males that fail to meet this requirement are inviable.

The males make up for the difference in X chromosome copy number by ensuring that each gene on their X chromosome is expressed at twice the rate of its equivalent on a female X, a phenomenon known as dosage compensation. The so-called Dosage Compensation Complex (DCC) is responsible for distinguishing the X chromosome from the others in males and doubling the level of activity of most of the genes it contains. The DCC is a complicated molecular machine which, in addition to so-called MSL proteins, contains two long RNA molecules (referred to as roX RNAs). "Correct incorporation of roX RNAs is known to be essential for DCC function, but how this is accomplished has been unclear," says LMU Professor Peter Becker, who studies how the operation of the DCC is regulated.

Switching to the binding mode

Members of his team have now discovered that a change in the structural conformation of the roX RNAs is a prerequisite for the functional activation of DCC. These RNAs all contain a characteristic hairpin structure, which is conserved in various fly species. "We have long supposed that such a widely conserved structure must be of functional significance, but we were unable to demonstrate a specific binding interaction between the hairpin and the MSL protein components of the DCC", Becker explains.

The reason for this is revealed in the new study. It turns out that the hairpin structure actually prevents protein binding. The hairpin must first be unwound by a specific enzyme before the MSL proteins can bind to the RNAs and a functional DCC is formed. The closed hairpin conformation is equivalent to a switch fixed in the OFF position. Unwinding of the flips the switch to ON, thus permitting assembly of the active DCC. "We believe that this switch is only activated under conditions that are found at certain sites on the X chromosome. This would ensure that dosage compensation is restricted to genes on the X", says Becker.

The researchers now assume that long RNAs play a much more active role in other regulatory complexes than has been suspected hitherto. Up to now, these RNAs have been seen as passive scaffolds for the binding of proteins. "We think though that they modulate the activity of the proteins they associate with. And we have now shown this for the DCC", Becker says. He will continue to work in this field. "Now it's getting really exciting," he says.

Explore further: Vermicompost leachate improves tomato seedling growth

More information: Molecular Cell, 2013. www.ncbi.nlm.nih.gov/pubmed/23870139

Related Stories

Meet CLAMP: A newly found protein that regulates genes

Jul 16, 2013

(Medical Xpress)—A newly discovered protein, found in many species, turns out to be the missing link that allows a key regulatory complex to find and operate on the lone X chromosome of male fruit flies, ...

X chromosome exposed

May 29, 2008

Researchers from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and the EMBL-European Bioinformatics Institute (EMBL-EBI) in Hinxton, UK, have revealed new insights into how sex chromosomes are regulated. ...

Molecular monkey arranges X-chromosome activation

Jul 25, 2013

X chromosomes are very special genetic material. They differ in number between men and women. To achieve equality between sexes, one out of two X chromosomes in women is silenced. In flies, the opposite happens: ...

New thinking on regulation of sex chromosomes in fruit flies

Sep 19, 2011

Fruit flies have been indispensible to our understanding of genetics and biological processes in all animals, including humans. Yet, despite being one of the most studied of animals, scientists are still finding the fruit ...

Recommended for you

Vermicompost leachate improves tomato seedling growth

Nov 21, 2014

Worldwide, drought conditions, extreme temperatures, and high soil saline content all have negative effects on tomato crops. These natural processes reduce soil nutrient content and lifespan, result in reduced plant growth ...

Plant immunity comes at a price

Nov 21, 2014

Plants are under permanent attack by a multitude of pathogens. To win the battle against fungi, bacteria, viruses and other pathogens, they have developed a complex and effective immune system. And just as ...

Evolution: The genetic connivances of digits and genitals

Nov 20, 2014

During the development of mammals, the growth and organization of digits are orchestrated by Hox genes, which are activated very early in precise regions of the embryo. These "architect genes" are themselves regulated by ...

Surrogate sushi: Japan biotech for bluefin tuna

Nov 20, 2014

Of all the overfished fish in the seas, luscious, fatty bluefin tuna are among the most threatened. Marine scientist Goro Yamazaki, who is known in this seaside community as "Young Mr. Fish," is working to ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.