News Release

Putting microRNAs in their place

Peer-Reviewed Publication

Cold Spring Harbor Laboratory

Scientists have discovered a novel protein complex that may help shed light on the function of a newly discovered class of small RNAs, as well as a common hereditary neurodegenerative disease.

An international research group, headed by Dr. Gideon Dreyfuss at UPENN School of Medicine, has successfully identified 31 novel very small RNAs, called microRNAs (miRNAs), and the protein complex that houses them. By identifying the protein components of this complex, the scientists were able to infer potential functions for the miRNAs with which they are associated.

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.

miRNAs have received considerable attention lately, owing to the realization of their widespread evolutionary distribution, and their similarity to other classes of small RNAs (approximately 22 nucleotides long) that are critical components of RNA interference and developmental gene regulation. Although over 100 miRNAs have been identified in organisms ranging from roundworms, to fruit flies, to humans, no one is quite sure what function they serve.

Dr. Dreyfuss’ work is providing some solid cues.

Dr. Dreyfuss and 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, the second most common childhood neuromuscular disorder.

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 common disease.

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