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Molecular biology

RNA strings and DNA parcels

Munich, 09/28/2012

The packaging of the DNA in the cell nucleus has an important influence on the control of gene function. LMU researchers have now shown that short RNA molecules play a critical role in regulating the accessibility of the genetic information.

 In higher organisms the genetic information is stored in a compact form in the nucleus of each cell. The double-stranded DNA molecules that make up the genome are wrapped around histone proteins to form a beads-on-a string like structure, that can be condensed further by interactions with other proteins. Collectively, these complexes comprise the “chromatin”. Before a gene sequence can be copied into single-stranded RNA, it must be made accessible to enzymes, and this is possible only if the relevant stretch of DNA lies in the relatively loosely packed fraction of chromatin named euchromatin.

A group of researchers led by LMU molecular biologist Axel Imhof and biochemist Gernot Längst from the University of Regensburg has now shown that, in the fruitfly Drosophila melanogaster, so-called snoRNAs play an important role in opening up the chromatin structure for transcription. snoRNAs are short RNAs found in the nucleus that were already known to act as cofactors in the localized chemical modification of other classes of RNA.

The recruiting agent
“Our studies also allowed us to determine how the RNAs bind to chromatin, and we identified a Drosophila protein called Decondensation factor 31 – Df31 for short – as the bridge between the snoRNAs and chromatin,” Imhof explains. Thus Df31 recruits snoRNA to specific sites in the chromatin, and is an important component of an RNA-protein network that is involved in the formation of the euchromatin fraction.

The new results could help to uncover the underlying causes of some forms of male infertility, as changes in the packaging of genomic DNA constitute a crucial aspect of spermatogenesis. “In flies, when Df31 is defective, the compact chromatin in the paternal nucleus fails to decondense properly after fertilization of the egg. It is quite possible that similar functions are required in mammalian systems,” says Imhof. (Molecular Cell, September 2012) göd


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