Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline

Gawande, Bharat; Robida, Mark D.; Rahn, Andrew; Singh, Ravinder

doi:10.1038/sj.emboj.7601022

Cited by 48 publications

(61 citation statements)

References 50 publications

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“…As Sxl is not present in males, CstF-64 can bind to the proximal pA signal and the smaller e(r) mRNA is synthesized. 43 Another example is the suppressor of forked, su(f), transcription unit. Three mRNAs are generated by alternative polyadenylation, of which the two longest result from the use of two pA sites in the 3'UTR, while the shorter transcript is produced using a pA site in intron 4 and does not produce a functional Su(f) protein.…”

Section: Regulation Of Mrna 3' End Formation By Protein Factorsmentioning

confidence: 99%

“…The enhancer of rudimentary, e(r), which has two pA signals in the 3'UTR, is illustrative of sex-specific alternative polyadenylation. The longer mRNA, e(r)-fs, using the distal pA signal is specifically expressed in adult females 43 by the RNA binding protein Sex-lethal (Sxl). A model has been proposed where in the female germline Sxl binds GU-rich elements in the proximal pA signal blocking its access to CstF-64, who then uses the distal pA signal instead and produces e(r)-fs mRNA.…”

Section: Regulation Of Mrna 3' End Formation By Protein Factorsmentioning

confidence: 99%

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Integrating transcription kinetics with alternative polyadenylation and cell cycle control

Moreira

2011

Nucleus

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Section: Regulation Of Mrna 3' End Formation By Protein Factorsmentioning

confidence: 99%

Section: Regulation Of Mrna 3' End Formation By Protein Factorsmentioning

confidence: 99%

Integrating transcription kinetics with alternative polyadenylation and cell cycle control

Moreira

2011

Nucleus

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“…The binding of CstF64 to the downstream uridine-rich element of a poly(A) site is a direct way to regulate a poly(A) site usage. For example, in the Drosophila female germ line, the RNA-binding protein SXL (sex-lethal) competes with CstF64 for binding to the uridine-rich element of the enhancer of rudimentary pre-mRNA and represses polyadenylation at the proximal poly(A) site (29). CstF64 binding is also pivotal in the choice of the proximal s poly(A) site of the immunoglobulin pre-mRNA during B cell differentiation (11).…”

Section: Discussionmentioning

confidence: 99%

Polypyrimidine Tract Binding Protein Prevents Activity of an Intronic Regulatory Element That Promotes Usage of a Composite 3′-Terminal Exon

Anquetil¹,

Sommer²,

Méreau

et al. 2009

Journal of Biological Chemistry

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Alternative splicing of 3-terminal exons plays a critical role in gene expression by producing mRNA with distinct 3-untranslated regions that regulate their fate and their expression. The Xenopus ␣-tropomyosin pre-mRNA possesses a composite internal/3-terminal exon (exon 9A9) that is differentially processed depending on the embryonic tissue. Exon 9A9 is repressed in non-muscle tissue by the polypyrimidine tract binding protein, whereas it is selected as a 3-terminal or internal exon in myotomal cells and adult striated muscles, respectively. We report here the identification of an intronic regulatory element, designated the upstream terminal exon enhancer (UTE), that is required for the specific usage of exon 9A9 as a 3-terminal exon in the myotome. We demonstrate that polypyrimidine tract binding protein prevents the activity of UTE in non-muscle cells, whereas a subclass of serine/arginine rich (SR) proteins promotes the selection of exon 9A9 in a UTE-dependent way. Morpholino-targeted blocking of UTE in the embryo strongly reduced the inclusion of exon 9A9 as a 3-terminal exon in the endogenous mRNA, demonstrating the function of UTE under physiological circumstances. This strategy allowed us to reveal a splicing pathway that generates a mRNA with no in frame stop codon and whose steady-state level is translation-dependent. This result suggests that a non-stop decay mechanism participates in the strict control of the 3-end processing of the ␣-tropomyosin pre-mRNA.Alternative splicing of 3Ј-terminal exons is a widespread mechanism in metazoans. Global in silico analysis showed that ϳ20% of human transcript units contain alternative 3Ј-terminal exons (1, 2). This process contributes to the complexity of gene expression by not only expanding the proteome through the generation of protein isoforms with distinct carboxyl-terminal domains but also producing mRNAs that differ in their 3Ј-untranslated region. These sequences are pivotal for determining the behavior of mRNA, since they are known to regulate translation, stability, and localization. The importance of the 3Ј-untranslated region in mRNA physiology was recently underscored by the identification of microRNAs that control the translation or half-life of mRNAs through interactions with sequences present within the 3Ј-untranslated region (3). Mechanistically, the regulation of 3Ј-terminal exon processing is very complex because it requires a coordinated control of the splicing and cleavage/polyadenylation reactions, the latter being tightly interconnected to transcription termination (4). At present, the factors and the mechanisms involved in the coupling between cleavage/polyadenylation and splicing remain largely unknown.Two classes of alternative 3Ј-terminal exons can be described based on the organization of the splice sites and the poly(A) site within the exon. The first class comprises exons that are delimited by a 3Ј splice site and a poly(A) site. Competition for inclusion between two such exons results in the production of mature mRNA with one of tw...

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“…Indeed, the large majority of the longer transcript is synthesized in the ovaries of the female. 14 In addition, the alternative polyadenylation of the e(r) transcript in the ovaries is regulated by Sex-lethal. 14 The pleiotropic effects of e(r) null mutations and their interaction with different genes point to the involvement of e(r) in a number of different pathways-pyrimidine biosynthesis (rudimentary 2 ), nerve cell specification (Notch 15 ), and ovarian development.…”

Section: Discussionmentioning

confidence: 99%

The Generation and Analysis of Deficiencies Within a Small Genomic rRegion on the X Chromosome ofDrosophila melanogasterContaining Two Genes,enhancer of rudimentaryandCG15352

Roykhman

Ibach²,

Harding³

et al. 2007

Fly

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KEy WoRDS enhancer of rudimentary, CG15352, P element mutagenesis ABBREVIATIoNS e(r) enhancer of rudimentary r rudimentary AcKNoWlEDGEMENTSThis work was supported by grants from the National Institutes of Health (R15 GM64364), Saint Louis University, the Monsanto Company (Monsanto Scholars Program) and SUNY Brockport. ABSTRAcTThe enhancer of rudimentary gene, e(r), encodes a 104-amino-acid, highly conserved transcription cofactor. Hypomorphic mutations of e(r) show an enhancement of a hypomorphic rudimentary mutant wing phenotype. These mutants in a wild-type background are viable, fertile, and morphologically wild-type. Since the only mutant alleles were hypomorphic, it was important to isolate null mutations to determine if any other phenotypes might be associated with a loss-of-function of e(r). We utilized a marked P element, P{SUPor-P, y + }, located 895 bp upstream of the start of transcription of e(r) to generate nineteen deficiencies in the region. Deficiencies of e(r) enhance the mutant wing phenotype of a hypomorphic rudimentary allele, r hd1 . In a wild-type background, the deficiencies of e(r), unlike the hypomorphic alleles, have a low viability and females have low fertility. The expression of e(r) in the nurse cells of the ovary is consistent with the low fertility, and suggests an ovarian function for e(r). Deficiencies of CG15352, the gene directly upstream of e(r), are not associated with any obvious mutant phenotypes and present the possibility that it encodes a nonvital or redundant function.

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Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline

Cited by 48 publications

References 50 publications

Integrating transcription kinetics with alternative polyadenylation and cell cycle control

Integrating transcription kinetics with alternative polyadenylation and cell cycle control

Polypyrimidine Tract Binding Protein Prevents Activity of an Intronic Regulatory Element That Promotes Usage of a Composite 3′-Terminal Exon

The Generation and Analysis of Deficiencies Within a Small Genomic rRegion on the X Chromosome ofDrosophila melanogasterContaining Two Genes,enhancer of rudimentaryandCG15352

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