Researchers solve piece of large-scale gene silenci...(w players necessary for the silencing ma...)

First in the pathway is RNA-dependent RNA Polymerase 2 (RDR2), which prepares a stretch of RNA for DICER-LIKE 3 (DCL3), an enzyme that chops up RNA transcripts into smaller segments. These smaller fragments of RNA become siRNAs, which then guide the de novo cytosine methyltransferase , DRM2, to the targeted genes. DRM2 is required to put a methyl group, a chemical flag that signals for silencing, on ribosomal genes that had been active in the parental genome. MBD6 and MBD10, methylcytosine binding proteins, then adhere to the segments of DNA that have been methylated by DRM2. At the same time, HDA6, a histone deacetylase, modifies the proteins that act as spools for the DNA.

The end result of this convergent, siRNA-mediated pathway is the large-scale silencing of hundreds of clustered rRNA genes that span millions of basepairs of DNA.

Nucleolar dominance occurs on a scale second only to X-chromosome inactivation, a process by which one of the two copies of the X-chromosome present in female mammals is randomly inactivated. Although nucleolar dominance is on a sub-chromosomal scale, it is, at least to date, "the largest scale gene silencing phenomenon that clearly seems to involve siRNAs," says Pikaard.

Pikaard explains, "siRNAs are not just regulating the selfish DNA or the junk DNA, but they're regulating the really essential genes too."

He believes that siRNAs might be the key to understanding the choice mechanism underlying which parental genes get switched off and which get left on, and he and his collaborators plan to investigate this possibility in future research.

"The truth is out there," says Pikaard.

'/>"/>