The small nuclear ribonucleoprotein biogenesis pathway

The small nuclear ribonucleoprotein biogenesis pathway. RNA polymerase II transcribes snRNAs as precursors containing an m7G cap and short 3′-end extensions in the nucleus. The cap-binding complex (CBC) binds nascent snRNAs and mediates the recruitment of the phosphorylated adaptor for RNA export (PHAX), exportin 1 (Xpo1) and ras-related nuclear protein GTP (RanGTP) for nuclear export. In the cytoplasm, the seven Sm proteins bind first to the chloride conductance regulatory protein (pICln) and the protein arginine methyltransferase 5 (PRMT5) complex—which symmetrically dimethylates SmB, SmD1 and SmD3—and then to the survival motor neuron (SMN) complex. The SMN complex bound to the Sm proteins interacts with snRNAs and mediates Sm core assembly. Hypermethylation of the 5′ cap of snRNAs by trimethylguanosine synthase 1 (TGS1) occurs after Sm core formation; both the SMN complex and snurportin, which associates with the 5′ cap of snRNAs, then bind to importin-β and mediate snRNP nuclear import. The SMN complex and snRNPs transiently localize to Cajal bodies, in which snRNPs undergo further maturation steps including methylation and pseudo-uridylation by small Cajal body-specific ribonucleoproteins (scaRNPs), before functioning in pre-messenger RNA splicing. Depending on the cell type and developmental stage, the SMN complex also localizes to Gems. snRNP, small nuclear ribonucleoprotein.

Publication

Chaperoning ribonucleoprotein biogenesis in health and disease. (2007) Livio Pellizzoni. EMBO Rep. 2007 Apr;8(4):340-345. Figure: F2. All organisms Drosophila melanogaster Homo sapiens

Disease mentions