The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1

Background: The survival of motor neurons (SMN) protein is the protein prod uct of the spinal muscular atrophy (SMA) disease gene. SMN and its associat ed proteins Gemin2, Gemin3, and Gemin4 form a large complex that plays a ro le in snRNP assembly, pre-mRNA splicing, and transcription. The functions o f SMN in these processes are mediated by a direct interaction of SMN with c omponents of these machineries, such as Sm proteins and RNA helicase A. Results: We show that SMN binds directly to fibrillarin and GAR1. Fibrillar in and GAR1 are specific markers of the two classes of small nucleolar ribo nucleoprotein particles (snoRNPs) that are involved in posttranscriptional processing and modification of ribosomal RNA. SMN interaction requires the arginine- and glycine-rich domains of both fibrillarin and GAR1 and is defe ctive in SMN mutants found in some SMA patients. Coimmunoprecipitations dem onstrate that the SMN complex associates with fibrillarin and with GAR1 in vivo. The inhibition of RNA polymerase I transcription causes a transient r edistribution of SMN to the nucleolar periphery and loss of fibrillarin and GAR1 colocalization with SMN in gems. Furthermore, the expression of a dom inant-negative mutant of SMN (SMN Delta N27) causes snoRNPs to accumulate o utside of the nucleolus in structures that also contain components of gems and coiled (Cajal) bodies. Conclusions: These findings identify fibrillarin and GAR1 as novel interact ors of SMN and suggest a function for the SMN complex in the assembly and m etabolism of snoRNPs. We propose that the SMN complex performs functions ne cessary for the biogenesis and function of diverse ribonucleoprotein comple xes.