Positive autoregulation of Sex-lethal by alternative splicing maintains the female determined state in Drosophila

Bell, Leslie; Horabin, Jamila I.; Schedl, Paul; Cline, Thomas W.

doi:10.1016/0092-8674(91)90157-t

Cited by 323 publications

(216 citation statements)

References 39 publications

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“…The interaction of Sxl with poly(U) motifs has been well-characterized biochemically and structurally (Inoue et al 1990;Valcárcel et al 1993;Handa et al 1999;Hennig et al 2014). In addition to its interaction with msl-2 mRNA (Bashaw and Baker 1995;Kelley et al 1995Kelley et al , 1997Bashaw and Baker 1997), Sxl also binds to poly(U) motifs present in its own mRNA (Cline 1984;Bell et al 1991) and in the transformer mRNA (tra) (Boggs et al, 1987). It is predicted to interact with hundreds of Drosophila RNAs containing analogous motifs (Medenbach et al 2011).…”

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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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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“…6A) is consistent with a potential autoregulatory mechanism involving atSRp30. Overproduced atSRp30 protein may stimulate the alternative splicing event, thus downregulating its own expression, as has been shown to be the case for several animal splicing factors, such as Sxl (Bell et al 1991), tra (Mattox and Baker 1991), and SWAP (Zachar et al 1987) from Drosophila, as well as mouse SRp20 . In agreement with this model, we could not detect a protein product from mRNA3 (atSRp30s).…”

Section: Is the Expression Of Atsrp30 Autoregulated?mentioning

confidence: 99%

atSRp30, one of two SF2/ASF-like proteins from Arabidopsis thaliana, regulates splicing of specific plant genes

Lopato¹,

Kalyna²,

Dorner³

et al. 1999

Genes & Development

150

199

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SR proteins are nuclear phosphoproteins with a characteristic Ser/Arg-rich domain and one or two RNA recognition motifs. They are highly conserved in animals and plants and play important roles in spliceosome assembly and alternative splicing regulation. We have now isolated and partially sequenced a plant protein, which crossreacts with antibodies to human SR proteins. The sequence of the corresponding cDNA and genomic clones from Arabidopsis revealed a protein, atSRp30, with strong similarity to the human SR protein SF2/ASF and to atSRp34/SR1, a previously identified SR protein, indicating that plants possess two SF2/ASF-like proteins. atSRp30 expresses alternatively spliced mRNA isoforms that are expressed differentially in various organs and during development. Overexpression of atSRp30 via a strong constitutive promoter resulted in changes in alternative splicing of several endogenous plant genes, including atSRp30 itself. Interestingly, atSRp30 overexpression resulted in a pronounced down-regulation of endogenous mRNA encoding full-length atSRp34/SR1 protein. Transgenic plants overexpressing atSRp30 showed morphological and developmental changes affecting mostly developmental phase transitions. atSRp30-and atSRp34/ SR1-promoter-GUS constructs exhibited complementary expression patterns during early seedling development and root formation, with overlapping expression in floral tissues. The results of the structural and expression analyses of both genes suggest that atSRp34/SR1 acts as a general splicing factor, whereas atSRp30 functions as a specific splicing modulator.

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“…4G) (22). Because Nito has three RRMs, we asked whether Nito has a potential role in Sxl splicing and used a pair of primers that detects the small female and large male spliced Sxl products (Fig.…”

Section: Nito Is a Ubiquitously Expressed Nuclear Protein That Is Crumentioning

confidence: 99%

spenito is required for sex determination in Drosophila melanogaster

Dong

Perrimon

2015

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

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Sex-lethal (Sxl) encodes the master regulator of the sex determination pathway in Drosophila and acts by controlling sex identity in both soma and germ line. In females Sxl maintains its own expression by controlling the alternative splicing of its own mRNA. Here, we identify a novel sex determination gene, spenito (nito) that encodes a SPEN family protein. Loss of nito activity results in stem cell tumors in the female germ line as well as female-to-male somatic transformations. We show that Nito is a ubiquitous nuclear protein that controls the alternative splicing of the Sxl mRNA by interacting with Sxl protein and pre-mRNA, suggesting that it is directly involved in Sxl auto-regulation. Given that SPEN family proteins are frequently mutated in cancers, our results suggest that these factors might be implicated in tumorigenesis through splicing regulation.germ-line stem cell | sex determination | alternative splicing S ex determination in Drosophila is under the control of the master regulatory gene Sex-lethal (Sxl) (1). Sxl acts downstream of the X-chromosome counting mechanism and encodes a female-specific RNA binding protein. Once activated, Sxl maintains its own expression by regulating the alternative splicing of its pre-mRNA. Sxl controls female fate by controlling somatic and germ-line sex identity as well as dosage compensation (2). In female somatic cells, Sxl controls the alternative splicing of transformer (tra), which together with transformer2 (tra2) controls the alternative splicing of doublesex (dsx) and fruitless (fru). dsx and fru in turn encode sex-specific transcription factors that control male versus female morphology, physiology, and behavior (3, 4). In addition, Sxl represses the male-specific dosage compensation system by regulating male-specific lethal 2 (msl-2) both at the level of alternative splicing and translational control (5

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Positive autoregulation of Sex-lethal by alternative splicing maintains the female determined state in Drosophila

Cited by 323 publications

References 39 publications

Specific RNP capture with antisense LNA/DNA mixmers

Specific RNP capture with antisense LNA/DNA mixmers

atSRp30, one of two SF2/ASF-like proteins from Arabidopsis thaliana, regulates splicing of specific plant genes

spenito is required for sex determination in Drosophila melanogaster

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