A Novel SR-Related Protein Is Required for the Second Step of Pre-mRNA Splicing

Cazalla, Demián; Newton, Keith; Cáceres, Javier F.

doi:10.1128/mcb.25.8.2969-2980.2005

Cited by 58 publications

(54 citation statements)

References 74 publications

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“…Many RNA processing factors, involved in either splicing or postsplicing processes such as mRNA export, nonsense-mediated decay, and polyadenylation, localize in speckles (16,(21)(22)(23)(24) and a speckled staining pattern indicates with near certainty a role in RNA processing (24)(25)(26). The virtually complete colocalization of bn2 with SC35 in nuclear speckles strongly suggests that bn2 has a function in RNA processing, and its unusual evolutionary stability implies that this function is essential.…”

Section: Discussionmentioning

confidence: 92%

Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely different properties and functions

Vanhoutteghem

Djian

2006

Proc. Natl. Acad. Sci. U.S.A.

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Basonuclin (bn) 1 possesses three separated pairs of zinc fingers and a nuclear localization signal. It is largely confined to the basal cells of stratified squamous epithelia and to reproductive germ cells. bn1 can shuttle between the nucleus and the cytoplasm, and its location is correlated with the proliferative potential of the cell. The recently discovered bn2 also possesses three separated pairs of zinc fingers and a nuclear localization signal. Conservation of the zinc fingers and the nuclear localization signal by bn1 and bn2 indicates a common origin. However, in contrast to bn1, bn2 is found in virtually every cell type and is confined to the nucleus. Bn2 but not bn1 colocalizes with SC35 in nuclear speckles and, therefore, is likely to have a function in nuclear processing of mRNA.RNA processing ͉ speckles ͉ zinc fingers B asonuclin (bn1) is a zinc finger protein with highly restricted tissue distribution: It is found mainly in basal keratinocytes of stratified squamous epithelium and in reproductive germ cells (1-5). bn1 possesses three separated pairs of zinc fingers, a nuclear localization signal (NLS) and a serine-rich region that has been called the serine stripe (1). Although the evidence is not conclusive, it seems that the function of bn1 is related to the potential for cell proliferation (6). The only known function of bn1 is that of a transcription factor in the synthesis of ribosomal RNA (7, 8), but it is possible that bn1 possesses a nucleoplasmic function in the regulation of expression of genes transcribed by RNA polymerase II (9).A gene encoding a second basonuclin (bn 2) recently has been discovered (10, 11). Although the deduced amino acid sequences of bn1 and bn2 are only slightly Ͼ40% identical, bn2 possesses all of the characteristic features of bn1 described above. The bn2 mRNA is abundant in cell types that possess bn1 but is also found in tissues that lack bn1, such as kidney, intestine, and uterus. The genes for bn1 and bn2 differ greatly in size and are located on different chromosomes, but it is clear that they have a common evolutionary origin. The evolutionary conservation of bn2 is much greater than that of bn1. It has been postulated that the gene for bn2 is the older of the two. After its duplication, the gene for bn1 was free to evolve in other directions, whereas the gene for bn2 remained virtually invariant (9, 11).Previous work on immunocytological detection of bn1 was carried out with polyclonal antisera raised against most or all of the bn1 protein (6, 12). In view of the similarities between bn1 and bn2, it was possible that these antisera did not distinguish between the two basonuclins. To detect each basonuclin independently, we generated antibodies to specific determinants not shared by bn1 and bn2. Using these antibodies, we show that, although the two basonuclins are of common origin, they possess widely different functions, because bn2 is likely to have a function in pre-mRNA processing. ResultsEvolutionary Conservation of bn2. We had reported that bn2 was e...

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Section: Discussionmentioning

confidence: 92%

Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely different properties and functions

Vanhoutteghem

Djian

2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Our finding that CAPER␣ preferentially associates with SF3b155 agrees with mass spectrometry findings that CAPER␣ is associated with catalytically active spliceosomes (4 -7). Furthermore, CAPER␣ is a known interaction partner of the SR-related alternative splicing factor, SRrp53, which is required for the second step of splicing (44).…”

Section: Discussionmentioning

confidence: 99%

Cancer-relevant Splicing Factor CAPERα Engages the Essential Splicing Factor SF3b155 in a Specific Ternary Complex

Loerch

Maucuer

Manceau

et al. 2014

Journal of Biological Chemistry

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Background: CAPER␣ contains a U2AF homology motif (UHM) that typically recognizes U2AF ligand motifs (ULM) of pre-mRNA splicing factors. Results: Crystal structures reveal CAPER␣ UHM/SF3b155 ULM interactions. CAPER␣ preferentially associates with the SF3b155 ULM-containing domain. Conclusion: CAPER␣ is recruited for pre-mRNA splicing via UHM/ULM interactions with SF3b155. Significance: Knowledge of CAPER␣/SF3b155 complexes will enhance understanding of angiogenic spliceoform regulation by CAPER␣.

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“…Mammalian hLuc7A is loosely associated with the human U1 snRNP and affects 5Ј ss selection by stabilizing U1 snRNP-premRNA interactions, as well as being involved in the formation of the E complex (36). Moreover, hLuc7A has recently been identified as a component of the supraspliceosome (9) and interacts with splicing factors RNPS1 (40) and SRrp53 (6).…”

Section: Discussionmentioning

confidence: 99%

Novel Splicing Factor RBM25 Modulates Bcl-x Pre-mRNA 5′ Splice Site Selection

Zhou

Cho

et al. 2008

Molecular and Cellular Biology

111

109

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RBM25 has been shown to associate with splicing cofactors SRm160/300 and assembled splicing complexes, but little is known about its splicing regulation. Here, we characterize the functional role of RBM25 in alternative pre-mRNA splicing. Increased RBM25 expression correlated with increased apoptosis and specifically affected the expression of Bcl-x isoforms. RBM25 stimulated proapoptotic Bcl-x S 5 splice site (5 ss) selection in a dose-dependent manner, whereas its depletion caused the accumulation of antiapoptotic Bcl-x L . Furthermore, RBM25 specifically bound to Bcl-x RNA through a CGGGCA sequence located within exon 2. Mutation in this element abolished the ability of RBM25 to enhance Bcl-x S 5 ss selection, leading to decreased Bcl-x S isoform expression. Binding of RBM25 was shown to promote the recruitment of the U1 small nuclear ribonucleoprotein particle (snRNP) to the weak 5 ss; however, it was not required when a strong consensus 5 ss was present. In support of a role for RBM25 in modulating the selection of a 5 ss, we demonstrated that RBM25 associated selectively with the human homolog of yeast U1 snRNP-associated factor hLuc7A. These data suggest a novel mode for Bcl-x S 5 ss activation in which binding of RBM25 with exonic element CGGGCA may stabilize the pre-mRNA-U1 snRNP through interactions with hLuc7A.Alternative splicing is a regulatory mechanism that allows eukaryotes to generate numerous protein isoforms, often with diverse biological functions, from a single gene (2,26,49). Pre-mRNA splicing takes place within the spliceosome, which is assembled stepwise by the addition of small nuclear ribonucleoprotein particles (snRNP) and numerous accessory nonsnRNP splicing factors (23, 31). The excision of introns and the joining of exons depend on the recognition and usage of 5Ј splice sites (5Ј ss) and 3Ј ss by the splicing machinery (21, 33). The commitment complex forms when the 5Ј ss is recognized by U1 snRNA base pairing and stabilized by U1 snRNP while the 3Ј ss is recognized by the U2 auxiliary factor (U2AF) through U2 snRNA base pairing with the branch point. Subsequently, the U4/5/6 tri-snRNP is incorporated into the complex and the U1 snRNA base paired at the 5Ј ss is replaced by U6 snRNA. These processes result in a fully assembled spliceosome that supports a series of rearrangements via RNA-RNA and RNA-protein interactions and activates the catalytic steps of cleavage, exon joining, and intron release (2, 26).However, the splice site signals that define the 5Ј ss and 3Ј ss are often degenerate. How and when they are used are believed to be modulated by a combinational interplay of positive (splicing enhancers) and negative (splicing silencers) cis elements and trans-acting factors (2, 26), forming the basis of alternative splicing. The splicing regulatory (SR) proteins (18, 41) and the heterogeneous nuclear ribonucleoproteins (hnRNPs) (11,46) bind with specificity to pre-mRNA (20).The SR proteins generally bind to enhancer elements through the RNA-binding domain and activate splicing at...

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A Novel SR-Related Protein Is Required for the Second Step of Pre-mRNA Splicing

Cited by 58 publications

References 74 publications

Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely different properties and functions

Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely different properties and functions

Cancer-relevant Splicing Factor CAPERα Engages the Essential Splicing Factor SF3b155 in a Specific Ternary Complex

Novel Splicing Factor RBM25 Modulates Bcl-x Pre-mRNA 5′ Splice Site Selection

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