2007
DOI: 10.1038/nsmb1303
|View full text |Cite
|
Sign up to set email alerts
|

prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast

Abstract: Prp8 protein is a highly conserved pre-mRNA splicing factor and a component of spliceosomal U5 snRNPs. Intriguingly, although it is ubiquitously expressed, mutations in the C-terminus of human Prp8p cause the retina-specific disease Retinitis pigmentosa (RP). The biogenesis of U5 snRNPs is poorly characterized. We present evidence for a cytoplasmic precursor U5 snRNP in yeast that lacks a mature U5 snRNP component, Brr2p, and depends on a nuclear localization signal in Prp8p for its efficient nuclear import. T… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

8
132
0
1

Year Published

2009
2009
2020
2020

Publication Types

Select...
4
4

Relationship

1
7

Authors

Journals

citations
Cited by 95 publications
(141 citation statements)
references
References 41 publications
8
132
0
1
Order By: Relevance
“…It is interesting to compare these findings with two recent studies performed in yeast (Boon, et al, 2007;Maeder, et al, 2009). Both studies showed that the mutations which cause RP in human patients, when present in yeast Prp8 protein, result in its reduced association with the DEAD-box helicase Brr2p in the yeast nucleus (Boon, et al, 2007;Maeder, et al, 2009).…”
Section: Discussionmentioning
confidence: 76%
See 2 more Smart Citations
“…It is interesting to compare these findings with two recent studies performed in yeast (Boon, et al, 2007;Maeder, et al, 2009). Both studies showed that the mutations which cause RP in human patients, when present in yeast Prp8 protein, result in its reduced association with the DEAD-box helicase Brr2p in the yeast nucleus (Boon, et al, 2007;Maeder, et al, 2009).…”
Section: Discussionmentioning
confidence: 76%
“…These data are all consistent with the hypothesis that PRPF8-RP is the result of presence of abnormal protein. However, in contrast, haploid yeast with H2387P, equivalent to the human H2309P mutation, have a growth sensitive phenotype, but the diploid heterozygous yeast grow completely normally (Boon, et al, 2007). This finding suggests that gene replacement therapy could still prove effective in this form of RP.…”
Section: Discussionmentioning
confidence: 81%
See 1 more Smart Citation
“…Fission yeast, however, encode clear Smn and Gemin2 orthologues (Hannus et al, 2000;Owen et al, 2000). Despite these facts, there is little evidence for a role for Smn in snRNP assembly in Schizosaccharomyces pombe (Hannus et al, 2000;Paushkin et al, 2000) or even for a cytoplasmic phase for Sm core assembly in Saccharomyces cerevisiae (Murphy et al, 2004;Boon et al, 2007). These and other findings (see below) suggest that Drosophila contains a primitive version of the mammalian SMN complex.…”
Section: Discussionmentioning
confidence: 81%
“…However, initial assembly of yeast U5 snRNP in the cytoplasm leads to a pre-U5 particle that contains the assembly factor Aar2 instead of Brr2. [34][35][36][37][38][39] Thus, Brr2 is transported to the nucleus independent of other U5 snRNP components 35 and its helicase activity may have to be shut off during this phase to avoid detrimental off-target effects. Once assembled in the nucleus, mature U5 snRNP joins the U4/U6 di-snRNP to form the U4/U6 U5 trisnRNP, in which Brr2 already encounters its U4/U6 di-snRNA substrate before incorporation into the spliceosome.…”
Section: Brr2 Requires Tight Regulationmentioning
confidence: 99%