Spinal muscular atrophy (SMA) is a common motor neuron disease and one of the leading genetic causes of death of young children. SMA is caused by deletions or loss of function mutations of the Survival of Motor Neurons (SMN) gene. The SMN protein associates with six additional proteins into an SMN complex and functions in the assembly of small nuclear ribonucleoproteins (snRNPs) and possibly other RNPs. MicroRNAs (miRNAs) are a newly discovered class of -22 nucleotide regulatory RNAs that are bound to Argonaute proteins. miRNAs act as specificity determinants to direct destruction or translational repression of their mRNA targets. miRNAs have the capacity to regulate numerous genes and they may exert profound effects in gene expression regulation. We have identified a novel RNP, termed microRNP (miRNP), that contains miRNAs, the Argonaute2 protein and the SMN complex proteins GeminS (an RNA helicase) and Gemin4. We propose to study the role of the SMN complex in the biogenesis and function of miRNAs and miRNPs. We will also study whether the biogenesis or function of miRNAs and miRNPs are dysregulated in SMA. Our work will likely uncover novel functions for the SMN complex and will also shed light in the function of miRNAs. Ultimately, investigations of the function of the SMN complex may lead to better understanding of the pathogenesis of SMA and possibly of other motor neuron diseases. ? ?
| Kirino, Yohei; Mourelatos, Zissimos (2007) Mouse Piwi-interacting RNAs are 2'-O-methylated at their 3'termini. Nat Struct Mol Biol 14:347-8 |
