The<i>Drosophila Hrb87F</i>gene encodes a new member of the A and B hnRNP protein group

Haynes, Susan R.; Johnson, Diana; Raychaudhuri, G; Beyer, Ann L.

doi:10.1093/nar/19.1.25

Cited by 65 publications

(66 citation statements)

References 51 publications

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“…As Dscam is essential for viability 5 , it is surprising that flies lacking hrp36 are viable 25,26 and that exon 6 splicing occurs normally in hrp36-null flies (S.O. and B.R.G., unpublished data).…”

Section: Discussionmentioning

confidence: 99%

A regulator of Dscam mutually exclusive splicing fidelity

Olson

Blanchette

Park

et al. 2007

Nat Struct Mol Biol

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The Down syndrome cell adhesion molecule (Dscam) gene has essential roles in neural wiring and pathogen recognition in Drosophila melanogaster. Dscam encodes 38,016 distinct isoforms via extensive alternative splicing. The 95 alternative exons in Dscam are organized into clusters that are spliced in a mutually exclusive manner. The exon 6 cluster contains 48 variable exons and uses a complex system of competing RNA structures to ensure that only one variable exon is included. Here we show that the heterogeneous nuclear ribonucleoprotein hrp36 acts specifically within, and throughout, the exon 6 cluster to prevent the inclusion of multiple exons. Moreover, hrp36 prevents serine/arginine-rich proteins from promoting the ectopic inclusion of multiple exon 6 variants. Thus, the fidelity of mutually exclusive splicing in the exon 6 cluster is governed by an intricate combination of alternative RNA structures and a globally acting splicing repressor.Pre-mRNA splicing is frequently used to regulate important biological processes. It is currently estimated that between 60% and 75% of human genes encode alternatively spliced pre-mRNAs 1,2 . Though most of these genes encode 2-3 different isoforms, there are several examples of genes that can generate much larger repertoires of mRNAs. For example, the human KCNMA1 gene can generate ~500 different isoforms, and the three NRXN genes together produce over 2,000 isoforms 3,4 . However, by far the most notable example is the D. melanogaster Dscam gene, which can generate 38,016 isoforms 5 .Correspondence should be addressed to B.R.G. (graveley@neuron.uchc.edu). (Fig. 1a). These variable exons are organized in clusters; the exon 4, 6, 9 and 17 clusters contain 12, 48, 33 and 2 variable exons, respectively. Importantly, the exons within each cluster are spliced in a mutually exclusive manner-only one exon from each cluster is included in the mRNA. The exon 4, 6 and 9 clusters encode alternative versions of extracellular immunoglobulin repeats, whereas the exon 17 cluster encodes two different transmembrane domains, such that each of the 38,016 isoforms has the same overall domain structure.From a mechanistic view one of the most puzzling aspects of Dscam is how the splicing of the large clusters of exons occurs in a mutually exclusive manner. Thousands of eukaryotic genes contain regions that have two mutually exclusive exons, and a variety of mechanisms are known that ensure that only one exon is included in these mRNAs. These mechanisms involve steric hindrance, the use of both the major and minor spliceosomes, and the nonsense-mediated decay pathway 15 . However, none of these mechanisms explain how the variable clusters in Dscam can be spliced in a mutually exclusive manner.Insight into the mechanism by which Dscam splicing occurs in a mutually exclusive manner was obtained from comparative genomics 16,17 . The exon 6 cluster contains two classes of conserved elements: the docking site, which is located in the intron downstream of constitutive exon 5, and the sele...

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Section: Discussionmentioning

confidence: 99%

A regulator of Dscam mutually exclusive splicing fidelity

Olson

Blanchette

Park

et al. 2007

Nat Struct Mol Biol

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“…These are splicing factors that share a high degree of homology with each other (Haynes et al 1991;Blanchette et al 2009). Sxl can interact with Hrb87F, most likely via its glycine-rich region, and it increases the affinity of Hrb87F for U-rich sequences .…”

Section: Specific Rnp Capture In Vitromentioning

confidence: 99%

Specific RNP capture with antisense LNA/DNA mixmers

Rogell

Fischer

Rettel

et al. 2017

RNA

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RNA-binding proteins (RBPs) play essential roles in RNA biology, responding to cellular and environmental stimuli to regulate gene expression. Important advances have helped to determine the (near) complete repertoires of cellular RBPs. However, identification of RBPs associated with specific transcripts remains a challenge. Here, we describe "specific ribonucleoprotein (RNP) capture," a versatile method for the determination of the proteins bound to specific transcripts in vitro and in cellular systems. Specific RNP capture uses UV irradiation to covalently stabilize protein-RNA interactions taking place at "zero distance." Proteins bound to the target RNA are captured by hybridization with antisense locked nucleic acid (LNA)/DNA oligonucleotides covalently coupled to a magnetic resin. After stringent washing, interacting proteins are identified by quantitative mass spectrometry. Applied to in vitro extracts, specific RNP capture identifies the RBPs bound to a reporter mRNA containing the Sex-lethal (Sxl) binding motifs, revealing that the Sxl homolog sister of Sex lethal (Ssx) displays similar binding preferences. This method also revealed the repertoire of RBPs binding to 18S or 28S rRNAs in HeLa cells, including previously unknown rRNA-binding proteins.

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“…Nts is a tightly linked gene that has not been characterized. Hrb87F encodes an RNA-binding protein similar to sqd (Haynes et al 1991;Matunis et al 1992b). B52 encodes a chromatin binding protein (Champlin et al 1991 ).…”

Section: Cloning Sqdmentioning

confidence: 99%

Initial organization of the Drosophila dorsoventral axis depends on an RNA-binding protein encoded by the squid gene.

Kelley¹

1993

Genes Dev.

127

107

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(Steward 1987, 19891 Doyle et al. 1989Roth et al. 1989;Rushlow et al. 1989;Ray et al. 1991). This subcellular distribution of D1 protein is determined by extraembryonic spatial cues received by the transmembrane Toll (T1) receptor in the early embryo (Hashimoto et al. 1988, 19911. These cues may be deposited in the vitelline membrane much earlier during oogenesis and act as a stable template on which the embryo organizes its body plan (Stein et al. 1991; Stem and Nfisslein-Volhard 1992).Although these late events are well characterized, little is known about the mechanism by which eggs initially generate D/V asymmetries during oogenesis. (Schiipbach 1987;Ashburner et al. 1990). These mutants are thought to be defective in the signaling pathway between the oocyte and follicle cells so that no follicle cell is able to acquire a dorsal fate. The opposite phenotype is observed in eggs and embryos derived from mothers mutant for fs(1) KlO (KIO), spire (spir), or cappuccino (capu) (Wieschaus et al. 1978; Manseau and Schfipbach 1989). These eggs are dorsalized and deficient in ventral structures. One possible interpretation of this phenotype is that too many follicle cells receive the dor- 948GENES & DEVELOPMENT 7:948-960 9 1993 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/93 $5.00Cold Spring Harbor Laboratory Press on May 12, 2018 -Published by genesdev.cshlp.org Downloaded from

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TheDrosophila Hrb87Fgene encodes a new member of the A and B hnRNP protein group

Cited by 65 publications

References 51 publications

A regulator of Dscam mutually exclusive splicing fidelity

A regulator of Dscam mutually exclusive splicing fidelity

Specific RNP capture with antisense LNA/DNA mixmers

Initial organization of the Drosophila dorsoventral axis depends on an RNA-binding protein encoded by the squid gene.

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