SMN (survival motor neuron protein) complexes are essential for the biogenesis of uridine-rich small nuclear ribonucleoproteins (UsnRNPs). During the biogenesis, the SMN complexes bound to UsnRNPs are transported from the cytoplasm to the nucleus, and moved to Cajal body (bodies)/Gems (Cajal/Gems) where the SMN complexes- UsnRNPs are subjected to additional chemical modifications and dissociated to the SMN complexes and the mature UsnRNPs. Although the mature UsnRNPs are assembled into spliceosome with newly transcribed pre-mRNA in the perichromatin fibrils at the chromatin, the role of the dissociated nuclear SMN complexes remains undetermined. In this study, we identified Friend of Prmt1 (FOP; chromatin target of Prmt1, CHTOP; C1orf77) as a novel component of the nuclear SMN complexes by the biotin affinity purification, coupled with the mass spectrometry-based protein identification. FOP was associated with SMN, Gemines 2, 3, 4, 6, and 8, unrip, and fragile X mental retardation 1 protein (FMR1), as well as with U5and U6 snRNAs in the nucleus, but not with Sm proteins, Gemin5, coilin, and U1 and U2snRNAs. Using the quantitative proteomic method with SILAC coupled with RNA interference, we also showed that FOP is required for the association of the SMN complexes with hnRNPs, histone proteins, and various RNA-binding proteins. It is reported that FOP localizes mainly in the nuclear speckles, binds chromatin, and plays a role in mRNA transcriptional regulation. Our present data suggest that the nuclear SMN complex containing FOP participates in the process of mRNA post-transcriptional regulation.

C1orf77, Chromatin target of Prmt1, CHTOP, Gemin, LC-MS/MS, SILAC, Smn, SRAG,
Journal of Proteomics and Bioinformatics
Biophysical Genomics, Department Cell Biology & Genetics

Izumikawa, K, Ishikawa, H, Yoshikawa, H, Terukina, G, Miyazawa, N, Nakayama, H, … Takahashi, N. (2014). Friend of Prmt1, FOP is a novel component of the nuclear SMN complex isolated using biotin affinity purification. Journal of Proteomics and Bioinformatics, 7(4). doi:10.4172/jpb.S7-002