Small nuclear ribonucleoproteins (snRNPs) are active in recognizing and removing introns from pre-mRNA in the nucleus. Each snRNP particle is composed of small nuclear RNA (snRNA) of approximately 150 nucleotides, several Sm proteins and a number of specific proteins that are unique for each snRNP. Survival motor neuron (SMN) functions in the cytoplasm to assemble Sm proteins onto the snRNAs to produce an active snRNP particle., , , .
A) In the cytoplasm the 7 Sm proteins bind to the chloride conductance regulatory protein (pICln)., In vitro studies reveal that pICIn first binds the Sm proteins as two separate complexes: SmB, SmD3, and SmD1, SmD2. The latter subsequently binds SmE, SmF and SmG The protein arginine methyltrasferase (PRMT5 complex) and PRMT7 methylate the Sm proteins SmB, SmD1 and SmD3.,,, Sm proteins are released from pICln-PRMT5 complex and bind the SMN complex.
B1) The SMN complex is composed of SMN, Gemins2-8 and unrip. SMN is shown in the figure as an oligomer as it has been shown to self-associate and it has been suggested that oligomerization is critical for SMN function (see text). The exact numbers of SMN monomers in a SMN complex is unknown (it has been suggested to be an octomer). The Gemins are shown as single units for simplicity as the exact stoichiometry of the SMN complex has not been determined.
B2) snRNA is transcribed in the nucleus and then binds the export proteins phosphorylated adaptor for RNA export (PHAX), Cap-binding complex (CBC), exportin (Xpo1) and ras-related nuclear protein GTP (Ran), which transport it to the cytoplasm. In vertebrates, the snRNA is brought into the Sm protein-bound SMN complex by binding to Gemin5.
C) The SMN complex places the Sm proteins onto the snRNA., The m7G cap of the snRNA is hypermethylated by trimethylguanosine sythetase 1 (TGS), allowing the SMN complex with the snRNA to bind snurportin and importin, which mediates transport of the SMN complex with an assembled snRNP into the nucleus.
D) In the nucleus the SMN complex and snRNPs localize to the Cajal body and snRNPs undergo further maturation. Depending on the cell type and developmental stage, SMN can localize as a separate body adjacent to the Cajal body.–
The figure is adapted from Pellizzoni.