5 January 2008. After messenger RNA, there were microRNAs, small noncoding RNAs that control the fate of messenger RNAs, and with them the growth and development of cells and organisms. Now there is a new RNA on the block. Longer than microRNAs but still noncoding, these abundant molecules were thought by some to be biologically relevant, and by others to represent transcriptional noise. An analysis of in-situ hybridization patterns for more than a thousand of these transcripts suggests that indeed many do have a functional role in the brain. The paper, published in PNAS Early Edition this week, comes from the lab of John Mattick from the University of Queensland in Australia.
Dual first authors Tim Mercer and Marcel Dinger looked at the expression of noncoding RNAs in the Allen Brain Atlas, a collection of in-situ hybridization data on mouse brain (Lien et al., 2007). In that dataset, researchers from the Allen Institute for Brain Science in Seattle, Washington, cataloged the expression patterns of roughly 20,000 genes. By analyzing the probe sequences, Mercer and Dinger determined that 1,328 of the probes most likely matched RNAs that did not encode proteins. Of these, 849 turned out to be functionally interesting, in that they were expressed in brain in a region-restricted or cell-specific manner, or were restricted to specific subcellular locations, just like many protein-coding RNAs. The transcripts came from a variety of genomic regions, including intergenic and intronic regions. Many overlapped with, or were transcribed antisense to genes known to function in the brain.
The analysis only looked at a small portion of the known noncoding transcripts in the brain, and the investigators estimate there could be up to 20,000 ncRNAs there that are processed and have a biological role. The study, they write, “represents an important early step in appreciating the significance of ncRNA in brain biology and not only provides compelling evidence that many of these transcripts are intrinsically functional, but also identifies many for future study.” To facilitate that future work, the investigators have compiled the data into a searchable, freely accessible online database.—Pat McCaffrey.
Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS. Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):716-21. Epub 2008 Jan 9. Abstract