Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR

Mihailovich, Marija; Wurth, Laurence; Zambelli, Federico; Abaza, Irina; Militti, Cristina; Mancuso, Francesco; Roma, Guglielmo; Pavesi, Giulio; Gebauer, Fátima

doi:10.1261/rna.029603.111

Cited by 21 publications

(19 citation statements)

References 37 publications

(55 reference statements)

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“…Thus, it would appear unlikely that UNR would bind to the conserved motif in the tra intron. Nevertheless, the possibility that UNR binds to tra transcripts should not be completely discounted given that UNR binds to many sex-specifically processed transcripts in Drosophila [23].Interestingly, the motif downstream of the most 5′ TRA/TRA2 site shows a partial (7/8 in Chtra ) match to the sequence [(5′-(U/G)GAAGAU(U/A)-3′] suggested by Verhulst et al [11] to be a potential binding site for TRA/TRA2 in Nasonia vitripennis and Apis mellifera . Alignment of the DNA sequences of the 3′ end of the intron identified a conserved type A RBP1 binding site (DCADCTTA) about 100 bp upstream of the splice acceptor site (Figure 4C, purple).…”

Section: Resultsmentioning

confidence: 99%

Conservation and Sex-Specific Splicing of the transformer Gene in the Calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata

Vensko

Belikoff

et al. 2013

PLoS ONE

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Transformer (TRA) promotes female development in several dipteran species including the Australian sheep blowfly Lucilia cuprina, the Mediterranean fruit fly, housefly and Drosophila melanogaster. tra transcripts are sex-specifically spliced such that only the female form encodes full length functional protein. The presence of six predicted TRA/TRA2 binding sites in the sex-specific female intron of the L. cuprina gene suggested that tra splicing is auto-regulated as in medfly and housefly. With the aim of identifying conserved motifs that may play a role in tra sex-specific splicing, here we have isolated and characterized the tra gene from three additional blowfly species, L. sericata, Cochliomyia hominivorax and C. macellaria. The blowfly adult male and female transcripts differ in the choice of splice donor site in the first intron, with males using a site downstream of the site used in females. The tra genes all contain a single TRA/TRA2 site in the male exon and a cluster of four to five sites in the male intron. However, overall the sex-specific intron sequences are poorly conserved in closely related blowflies. The most conserved regions are around the exon/intron junctions, the 3′ end of the intron and near the cluster of TRA/TRA2 sites. We propose a model for sex specific regulation of tra splicing that incorporates the conserved features identified in this study. In L. sericata embryos, the male tra transcript was first detected at around the time of cellular blastoderm formation. RNAi experiments showed that tra is required for female development in L. sericata and C. macellaria. The isolation of the tra gene from the New World screwworm fly C. hominivorax, a major livestock pest, will facilitate the development of a “male-only” strain for genetic control programs.

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Section: Resultsmentioning

confidence: 99%

Conservation and Sex-Specific Splicing of the transformer Gene in the Calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata

Vensko

Belikoff

et al. 2013

PLoS ONE

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“…RIP-Seq of Drosophila UNR in male and female flies identified a pronounced sex-specific binding bias for this protein; follow-up RNA-Seq experiments correlated UNR binding with the sex-specific alternative processing of UTRs in target messages [51]. Processing of UTRs, and specially of the 3′-UTR, has been proposed to importantly contribute to global gene expression regulation.…”

Section: Rbps Go ‘Omics’mentioning

confidence: 99%

Translational control by 3'-UTR-binding proteins

Szóstak¹,

Gebauer²

2012

Briefings in Functional Genomics

148

127

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The regulation of mRNA translation is a major checkpoint in the flux of information from the transcriptome to the proteome. Critical for translational control are the trans-acting factors, RNA-binding proteins (RBPs) and small RNAs that bind to the mRNA and modify its translatability. This review summarizes the mechanisms by which RBPs regulate mRNA translation, with special focus on those binding to the 3′-untranslated region. It also discusses how recent high-throughput technologies are revealing exquisite layers of complexity and are helping to untangle translational regulation at a genome-wide scale.

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“…The centrosome and control of mitosis were also significantly enriched terms (n=11). Recent studies identified Csde1 targets in melanoma cells and Drosophila melanogaster 20,36 . Comparison showed that 53 of the 274 transcripts we identified as Csde1-associated transcripts were also identified as a Csde1 target in melanoma cells using iCLIP 20 .…”

Section: Resultsmentioning

confidence: 99%

Csde1 binds transcripts involved in protein homeostasis and controls their expression in erythropoiesis

Moore

Yagci

Alphen

et al. 2017

Preprint

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Expression of the RNA-binding protein Csde1 (Cold shock domain protein e1) is strongly upregulated during erythropoiesis compared to other hematopoietic lineages. In the severe congenital anemia Diamond Blackfan Anemia (DBA), however, Csde1 expression is impaired. Reduced expression of Csde1 in healthy erythroblasts impaired their proliferation and differentiation, which suggests an important role for Csde1 in erythropoiesis. To investigate the cellular pathways controlled by Csde1 in erythropoiesis, we identified the transcripts that physically associate with Csde1 in erythroid cells. These mainly encoded proteins involved in ribogenesis, mRNA translation and protein degradation, but also proteins associated with the mitochondrial respiratory chain and mitosis. Crispr/Cas9-mediated deletion of the first cold shock domain of Csde1 affected RNA expression and/or protein expression of Csde1-bound transcripts. For instance, protein expression of Pabpc1 was enhanced while Pabpc1 mRNA expression was reduced indicating more efficient translation of Pabpc1 followed by negative feedback on mRNA stability. Overall, the effect of reduced Csde1 function on mRNA stability and translation of Csde1-bound transcripts was modest. Clones with complete loss of Csde1, however, could not be generated. We suggest that Csde1 is involved in feed-back control in protein homeostasis and that it dampens stochastic changes in mRNA expression.

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Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR

Cited by 21 publications

References 37 publications

Conservation and Sex-Specific Splicing of the transformer Gene in the Calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata

Conservation and Sex-Specific Splicing of the transformer Gene in the Calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata

Translational control by 3'-UTR-binding proteins

Csde1 binds transcripts involved in protein homeostasis and controls their expression in erythropoiesis

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