The testis-specific double bromodomain-containing protein BRDT forms a complex with multiple spliceosome components and is required for mRNA splicing and 3'-UTR truncation in round spermatids.

Nucleic Acids Research
Binyamin D BerkovitsDebra J Wolgemuth

Abstract

Members of the BET (bromodomain and extra terminal motif) family of proteins have been shown to be chromatin-interacting regulators of transcription. We previously generated a mutation in the testis-specific mammalian BET gene Brdt (bromodomain, testis-specific) that yields protein lacking the first bromodomain (BRDT(ΔBD1)) and observed disrupted spermiogenesis and male sterility. To determine whether BRDT(ΔBD1) protein results in altered transcription, we analyzed the transcriptomes of control versus Brdt(ΔBD1/ΔBD1) round spermatids. Over 400 genes showed statistically significant differential expression, and among the up-regulated genes, there was an enrichment of RNA splicing genes. Over 60% of these splicing genes had transcripts that lacked truncation of their 3'-untranslated region (UTR) typical of round spermatids. We selected four of these genes to characterize: Srsf2, Ddx5, Hnrnpk and Tardbp. The 3'-UTRs of Srsf2, Ddx5 and Hnrnpk mRNAs were longer in mutant round spermatids and resulted in reduced protein levels. Tardbp was transcriptionally up-regulated and a splicing shift toward the longer variant was observed. All four splicing proteins were found to complex with BRDT in control and mutant testes. We thus suggest t...Continue Reading

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Citations

Jul 17, 2013·Human Reproduction Update·Meritxell JodarUNKNOWN Reproductive Medicine Network
Mar 22, 2014·Expert Opinion on Therapeutic Targets·Mauricio BudiniEmanuele Buratti
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Jul 25, 2021·Cancers·Samuel P BoysonKaren C Glass

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Datasets Mentioned

BETA
GSE33132

Methods Mentioned

BETA
Chip
PCR
chips
pull-down
co-immunoprecipitation
Co-IP

Software Mentioned

Database for Annotation , Visualization and Integrated Discove...
DAVID
Bioconductor
limma
adjPVal
R
Gene Chip Robust Multiarray Algorithm ( RMA

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