Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5'-ends of all Kinetoplastid mRNAs consist of a short sequence added by trans splicing. In contrast to cis splicing in mammals, trans splicing in trypanosomes does not involve sequence-specific recognition of the branch point by the U2 snRNP. In mammalian cells and yeast, U2 snRNP is associated with the multimeric factor SF3b, which contains p14, SF3b10, SF3b14b, SAP49, SAP130, SAP145 and SAP155. The interaction between Trypanosoma cruzi p14 and SAP155 has already been characterised using the yeast 2-hybrid system. We here identify the Trypanosoma brucei RRM-protein DRBD1 as a homologue of SAP49. TAP-tagged DRBD1 co-purified with homologues of p14, SAP130, SAP145 and SAP155. Tagged DRBD1 was found in the nucleus; RNAi targeting DRBD1 inhibited trypanosome growth and caused a very mild splicing defect.
Mol Biochem Parasitol 2009 Aug
PMID:DRBD1 is the Trypanosoma brucei homologue of the spliceosome-associated protein 49. 1945 Jul 35

The interaction between splicing factors and the transcriptional machinery provides an intriguing link between the coupled processes of transcription and splicing. Here, we show that the two components of the SF3B complex, SF3B3 and SF3B5, that form part of the U2 small nuclear ribonucleoprotein particle (snRNP) are also subunits of the Spt-Ada-Gcn5 acetyltransferase (SAGA) transcriptional coactivator complex in Drosophila melanogaster. Whereas SF3B3 had previously been identified as a human SAGA subunit, SF3B5 had not been identified as a component of SAGA in any species. We show that SF3B3 and SF3B5 bind to SAGA independent of RNA and interact with multiple SAGA subunits including Sgf29 and Spt7 in a yeast two-hybrid assay. Through analysis of sf3b5 mutant flies, we show that SF3B5 is necessary for proper development and cell viability but not for histone acetylation. Although SF3B5 does not appear to function in SAGA's histone-modifying activities, SF3B5 is still required for expression of a subset of SAGA-regulated genes independent of splicing. Thus, our data support an independent function of SF3B5 in SAGA's transcription coactivator activity that is separate from its role in splicing.
J Mol Biol 2016 09 11
PMID:The Spliceosomal Protein SF3B5 is a Novel Component of Drosophila SAGA that Functions in Gene Expression Independent of Splicing. 2718 60

SF3b is a heptameric protein complex of the U2 small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. Mutations in the largest SF3b subunit, SF3B1/SF3b155, are linked to cancer and lead to alternative branch site (BS) selection. Here we report the crystal structure of a human SF3b core complex, revealing how the distinctive conformation of SF3b155's HEAT domain is maintained by multiple contacts with SF3b130, SF3b10, and SF3b14b. Protein-protein crosslinking enabled the localization of the BS-binding proteins p14 and U2AF65 within SF3b155's HEAT-repeat superhelix, which together with SF3b14b forms a composite RNA-binding platform. SF3b155 residues, the mutation of which leads to cancer, contribute to the tertiary structure of the HEAT superhelix and its surface properties in the proximity of p14 and U2AF65. The molecular architecture of SF3b reveals the spatial organization of cancer-related SF3b155 mutations and advances our understanding of their effects on SF3b structure and function.
Mol Cell 2016 10 20
PMID:Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations. 2772 Jun 43