Evidence that Dim1 associates with proteins involved in pre-mRNA splicing, and delineation of residues essential for Dim1 interactions with hnRNP F and Npw38/PQBP-1

Zhang, Yuzhu; Lindblom, Tim; Chang, Alex; Sudol, Marius; Sluder, Ann E.; Golemis, Erica A.

doi:10.1016/s0378-1119(00)00372-3

Cited by 67 publications

(75 citation statements)

References 30 publications

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“…In the nucleus, the N-terminal WW domain binds to the splicing factor WBP11 (ref. 9), whereas the C-terminal YxxPxxVL motif binds to the spliceosomal protein U5-15kD [6][7][8] . PQBP1, WBP11 and U5-15kD are all components of the precatalytic B complex 4,5 , and thus PQBP1 probably binds to both WBP11 and U5-15kD in the B complex.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5–15kD

et al. 2014

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A loss-of-function of polyglutamine tract-binding protein 1 (PQBP1) induced by frameshift mutations is believed to cause X-linked mental retardation. However, the mechanism by which structural changes in PQBP1 lead to mental retardation is unknown. Here we present the crystal structure of a C-terminal fragment of PQBP1 in complex with the spliceosomal protein U5-15kD. The U5-15kD hydrophobic groove recognizes a YxxPxxVL motif in PQBP1, and mutations within this motif cause a loss-of-function phenotype of PQBP1 in vitro. The YxxPxxVL motif is absent in all PQBP1 frameshift mutants seen in cases of mental retardation. These results suggest a mechanism by which the loss of the YxxPxxVL motif could lead to the functional defects seen in this type of mental retardation.

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Section: Discussionmentioning

confidence: 99%

Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5–15kD

et al. 2014

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“…We previously found that the WWD of PQBP1 interacts with the C-terminal domain of the large subunit of RNA polymerase II and that PQBP1 affects gene expression at the transcription level (Okazawa et al, 2002). We also found that PQBP1 interacts with a splicing factor U5-15KD (Waragai et al, 2000;Zhang et al, 2000); thus, PQBP1 may affect gene expression through posttranscriptional regulation. Therefore, we suspected that repression of a certain target gene in PNs of the dPQBP1-mutant flies might lead to learning disturbance.…”

Section: Nr1 Mediates Learning Disturbance Of Pqbp1-mutant Fliesmentioning

confidence: 91%

DrosophilaPQBP1 Regulates Learning Acquisition at Projection Neurons in Aversive Olfactory Conditioning

Tamura

Horiuchi²,

Chen³

et al. 2010

J. Neurosci.

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Polyglutamine tract-binding protein-1 (PQBP1) is involved in the transcription-splicing coupling, and its mutations cause a group of human mental retardation syndromes. We generated a fly model in which the Drosophila homolog of PQBP1 (dPQBP1) is repressed by insertion of piggyBac. In classical odor conditioning, learning acquisition was significantly impaired in homozygous piggyBac-inserted flies, whereas the following memory retention was completely normal. Mushroom bodies (MBs) and antennal lobes were morphologically normal in dPQBP1-mutant flies. Projection neurons (PNs) were not reduced in number and their fiber connections were not changed, whereas gene expressions including NMDA receptor subunit 1 (NR1) were decreased in PNs. Targeted double-stranded RNAmediated silencing of dPQBP1 in PNs, but not in MBs, similarly disrupted learning acquisition. NR1 overexpression in PNs rescued the learning disturbance of dPQBP1 mutants. HDAC (histone deacetylase) inhibitors, SAHA (suberoylanilide hydroxamic acid) and PBA (phenylbutyrate), that upregulated NR1 partially rescued the learning disturbance. Collectively, these findings identify dPQBP1 as a novel gene regulating learning acquisition at PNs.

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“…The fraction of unlabeled proteins probably comprises GYF-independent interactions of U5-15K, several of which were described previously (35).…”

Section: Table I Proteins Found In the Pulldown Experiments Compared mentioning

confidence: 94%

Proline-rich Sequence Recognition

Kofler

Schuemann

Merz

et al. 2009

Molecular & Cellular Proteomics

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The two catalytic steps of splicing are a conceptually simple process that results in the RNA-mediated excision of introns (1). Complexity arises at the level of RNA-RNA and protein-RNA interactions that are needed for the correct spatial positioning of the critical bases, unwinding of RNA, and coupling of splicing to other processes as for example transcription (2, 3), nonsense-mediated mRNA decay (4), or mRNA transport (5, 6). Pre-mRNA splicing is catalyzed by the spliceosome, a dynamic macromolecular machine, which consists of the small nuclear ribonuclear particles (snRNPs), 1 U1, U2, U4/U6, and U5, and numerous non-snRNP proteins (7). The snRNPs interact with the intron in an ordered manner. First the U1 snRNP binds to the 5Ј splice site, whereas the U2 snRNP stably associates with the branch site forming complex A. Subsequently the tri-snRNP U4/U6.U5 is stably integrated to form complex B. This complex undergoes large structural rearrangements that lead to the formation of the activated spliceosomal complex B*. The catalytic steps of the transesterification then occur in complex C. Proline-rich sequences (PRS) are frequently found in spliceosomal proteins, and they are mostly assigned to unstructured regions of the corresponding full-length proteins (8). They serve as docking sites for so-called proline-rich sequence recognition domains (PRDs), and their interactions are characterized by low affinities and moderate specificities (9 -13). Several of the interactions between PRD and their proline-rich binding sites within the spliceosome have been characterized in vitro in great detail, but little is known about their functional importance. One interesting spliceosomal protein that mediates PRS interactions is CD2BP2/52K (14). It is a component of the U5 snRNP (15, 16) and contains a GYF adaptor domain that recognizes PRS via a set of conserved aromatic amino acids (17)(18)(19). A likely interaction partner of the GYF domain is the core splicing protein SmB/BЈ, which is present in all snRNPs. The GYF domain of CD2BP2/52K comprises a second interaction surface on a site opposite to the PRS binding epitope. This site is bound by the essential splicing protein U5-15K (16, 20). Considering that the U5 snRNP protein Prp6 interacts with the N-terminal part of CD2BP2/52K (16), several independent interactions seemingly contribute to the association of the protein with the U5 snRNP. However, for the GYF domain we could identify by phage display and peptide SPOT analysis additional interaction sites in other proteins suggesting that further "moonlighting" functions of the GYF domain might exist (21,22). This has set the basis for the current study where we performed pulldown experiments to define more generally the importance of CD2BP2/52K-GYF for the assembly of protein complexes. Utilizing the GYF domain fused to GST as bait, a large number of protein components of the U1, U2, U5, and the U4/U6.U5 tri-snRNP were co-precipitated. The association of most proteins was highly dependent on the PRS binding site in the GY...

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Evidence that Dim1 associates with proteins involved in pre-mRNA splicing, and delineation of residues essential for Dim1 interactions with hnRNP F and Npw38/PQBP-1

Cited by 67 publications

References 30 publications

Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5–15kD

Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5–15kD

DrosophilaPQBP1 Regulates Learning Acquisition at Projection Neurons in Aversive Olfactory Conditioning

Proline-rich Sequence Recognition

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