MicroRNAs Linked to Neurodegenerative Disease

Results from the study of a novel protein complex may help shed light on the function of a newly discovered class of small RNAs. These "microRNAs” have been implicated in the development of spinal muscular atrophy, a hereditary neurodegenerative disease that is the second most common childhood neuromuscular disorder.

An international research group headed by Dr. Gideon Dreyfuss at the University of Pennsylvania School of Medicine (Philadelphia, USA) has identified 31 novel microRNAs (miRNAs), and the protein complex that houses them. Lately, miRNAs have received considerable attention, as they demonstrate widespread evolutionary distribution and are similar to other classes of small RNAs (approximately 22 nucleotides long) that are critical components of RNA interference and developmental gene regulation. So far, no function has been attributed to any of the miRNAs.

RNA transcripts do not exist as free molecules in the cell nucleus. Rather, RNAs exist in human cells as part of large ribonucleoprotein particles (RNPs) that contain various proteins. Dr. Dreyfuss and his colleagues found that the main protein components of the miRNPs are a eukaryotic translation initiation factor (eIF2C2) and previously identified components of the survival of motor neurons (SMN) complex, Gemin3 and Gemin4.

The presence of eIF2C2, an argonaute protein family member, in miRNPs confirms existing data implicating argonaute proteins in small RNA function. The presence of Gemin3 and 4, though, was a bit more surprising. The SMN complex is named for one of its main constituents, the survival of motor neurons protein, which, when mutated, results in spinal muscular atrophy. This finding of shared components between the SMN complex and the miRNP suggests a possible link between the pathway of miRNA activity and the progression of this disease.