Most of the DNA in the nucleus of each of our cells is converted into RNA, but only a small fraction of these RNA molecules serve as coding templates for the synthesis of proteins.
Of the remaining RNAs, known as "non-coding" RNAs (ncRNA), the functions of a scant few are known: they inhibit the activity of genes or modify them by altering the way in which DNA is packaged within cells. What the rest of them do within cells is largely a mystery.
Professor David L. Spector, Ph.D., and a team led by graduate student Hongjae Sunwoo at Cold Spring Harbor Laboratory (CSHL), have expanded our knowledge of ncRNA functions by uncovering a unique structure-building role for two ncRNA molecules. In a paper published in the March 1st issue of Genome Research , they show that ncRNAs called MENå and MENâ organize and maintain the structure of paraspeckles, a compartment within the cell's nucleus.
RNAs as structural components
Unlike its counterparts in simple organisms like yeast, the nucleus in mammalian cells has an extraordinarily complicated internal structure. In addition to the DNA-protein complex known as chromatin, the nucleus is organized with compartments such as the nucleolus, PML bodies, Cajal bodies, and many others. Cell biologists have long wondered how these compartments are organized, knowing only that each has a definite and precise form despite not being bound and contained within a membrane.
"The idea that some of these structures might somehow be supported by RNA molecules first surfaced in studies in the 1970s," according to Professor Spector. His lab found further evidence for this idea in 2005 when they showed that paraspeckles – each nucleus has about 10 to 30 of these scattered around – fell apart when cells were treated with an enzyme that destroys RNA. "But," Spector says, "a specific RNA molecule that gives paraspeckles their structural integrity was never found."
Spector, who is an avid explorer of ncRNAs and their activities in cells, thought ncRNAs were a good candidate for such a role, especially since many of them stay in the nucleus instead of getting expelled into the cell's cytoplasm like their protein-coding RNA cousins.
ncRNAs localize to paraspeckles
Cells usually increase their production of ncRNAs when they ramp up their metabolic activity – for example, when they differentiate during development. For this reason, Spector's team, in collaboration with John Mattick's laboratory (Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia), hunted for their ncRNA quarry in a type of stem cell that differentiates into muscle fibers. They narrowed their focus to 14 confirmed ncRNAs, each of which was produced at levels that were at least two times higher or lower in the differentiated cells.
"One way to figure out hints as to what ncRNAs do is to find out where they localize within cells, which might reveal the molecules they interact with and the pathways they participate in," explains Spector. Using a technique that uses a fluorescence signal to tag molecules within cells, Spector's team traced two of their 14 ncRNAs to paraspeckles, tiny compartments that look like dense dots anchored within the nucleus.
MENå and MENâ are structural organizers