title: Post-transcriptional modification of spliceosomal RNAs is normal in SMN-deficient cells.
abstract: The survival of motor neuron (SMN) protein plays an important role in the biogenesis of spliceosomal snRNPs and is one factor required for the integrity of nuclear Cajal bodies (CBs). CBs are enriched in small CB-specific (sca) RNAs, which guide the formation of pseudouridylated and 2'-O-methylated residues in the snRNAs. Because SMN-deficient cells lack typical CBs, we asked whether the modification of internal residues of major and minor snRNAs is defective in these cells. We mapped modified nucleotides in the major U2 and the minor U4atac and U12 snRNAs. Using both radioactive and fluorescent primer extension approaches, we found that modification of major and minor spliceosomal snRNAs is normal in SMN-deficient cells. Our experiments also revealed a previously undetected pseudouridine at position 60 in human U2 and 2'-O-methylation of A1, A2, and G19 in human U4atac. These results confirm, and extend to minor snRNAs, previous experiments showing that scaRNPs can function in the absence of typical CBs. Furthermore, they show that the differential splicing defects in SMN-deficient cells are not due to failure of post-transcriptional modification of either major or minor snRNAs.
authors: Carnegie Institution, Baltimore, Maryland 21218, USA.
authors: Svetlana
authors: S
authors: Deryusheva
authors: Maria
authors: M
authors: Choleza
authors: Adrien
authors: A
authors: Barbarossa
authors: Joseph G
authors: JG
authors: Gall
authors: Rémy
authors: R
authors: Bordonné
mesh_terms: D020541:Coiled Bodies / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: D012342:RNA, Small Nuclear; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; C405484:U2 small nuclear RNA