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Genome-wide analysis of gene expression and intron retention during development in a U12-type splicing-deficient zebrafish mutant

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Danio rerio

PROVIDER: GSE53935 | GEO | 2014/02/05

SECONDARY ACCESSION(S): PRJNA236230

REPOSITORIES: GEO

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Genome-wide analysis of gene expression and intron retention during development in a U12-type splicing-deficient zebrafish mutant

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-02-05 | E-GEOD-53935 | biostudies-arrayexpress

Genome-wide analysis of gene expression and intron retention during development in a U12-type splicing-deficient zebrafish mutant [RNA-seq]

Project description:To determine the global impact of the clbn mutation on gene expression and efficiency of U2- and U12-type splicing, we analyzed the transcriptome of 108hpf wt and clbn mutant larvae by microarrays and RNA sequencing. RNAseq data was used to characterize intron retention of U2-type and U12-type intron on a genome-wide scale to confirm that rnpc3 deficiency specifically impairs U12-type splicing. RNAseq and microarray data were combined to yield high-confidence lists of differentially expressed genes which show that impaired U12-type splicing has a wide-ranging effect on the developing transcriptome.

2014-02-05 | GSE53758 | GEO

Genome-wide analysis of gene expression and intron retention during development in a U12-type splicing-deficient zebrafish mutant [RNA-seq]

2014-02-05 | E-GEOD-53758 | biostudies-arrayexpress

Genome-wide analysis of gene expression and intron retention during deveopment in a U12-type splicing-deficient zebrafish mutant [microarray]

2014-02-05 | GSE53934 | GEO

Genome-wide analysis of gene expression and intron retention during deveopment in a U12-type splicing-deficient zebrafish mutant [microarray]

2014-02-05 | E-GEOD-53934 | biostudies-arrayexpress

Genome-wide analysis of gene expression and intron retention during development in a U12-type splicing-deficient zebrafish mutant

Project description:Genome-wide analysis of gene expression and intron retention during development in a U12-type splicing-deficient zebrafish mutant

| PRJNA236230 | ENA

Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective <i>Zrsr1</i> Mutant Mice.

Project description:Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior.

| S-EPMC6678158 | biostudies-literature

Role of the 3' splice site in U12-dependent intron splicing.

Project description:U12-dependent introns containing alterations of the 3' splice site AC dinucleotide or alterations in the spacing between the branch site and the 3' splice site were examined for their effects on splice site selection in vivo and in vitro. Using an intron with a 5' splice site AU dinucleotide, any nucleotide could serve as the 3'-terminal nucleotide, although a C residue was most active, while a U residue was least active. The penultimate A residue, by contrast, was essential for 3' splice site function. A branch site-to-3' splice site spacing of less than 10 or more than 20 nucleotides strongly activated alternative 3' splice sites. A strong preference for a spacing of about 12 nucleotides was observed. The combined in vivo and in vitro results suggest that the branch site is recognized in the absence of an active 3' splice site but that formation of the prespliceosomal complex A requires an active 3' splice site. Furthermore, the U12-type spliceosome appears to be unable to scan for a distal 3' splice site.

| S-EPMC86782 | biostudies-literature

Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome.

Project description:Somatic mutations in the spliceosome gene ZRSR2-located on the X chromosome-are associated with myelodysplastic syndrome (MDS). ZRSR2 is involved in the recognition of 3'-splice site during the early stages of spliceosome assembly; however, its precise role in RNA splicing has remained unclear. Here we characterize ZRSR2 as an essential component of the minor spliceosome (U12 dependent) assembly. shRNA-mediated knockdown of ZRSR2 leads to impaired splicing of the U12-type introns and RNA-sequencing of MDS bone marrow reveals that loss of ZRSR2 activity causes increased mis-splicing. These splicing defects involve retention of the U12-type introns, while splicing of the U2-type introns remain mostly unaffected. ZRSR2-deficient cells also exhibit reduced proliferation potential and distinct alterations in myeloid and erythroid differentiation in vitro. These data identify a specific role for ZRSR2 in RNA splicing and highlight dysregulated splicing of U12-type introns as a characteristic feature of ZRSR2 mutations in MDS.

| S-EPMC4349895 | biostudies-literature

The minor spliceosomal protein U11/U12-31K is an RNA chaperone crucial for U12 intron splicing and the development of dicot and monocot plants.

Project description:U12 intron-specific spliceosomes contain U11 and U12 small nuclear ribonucleoproteins and mediate the removal of U12 introns from precursor-mRNAs. Among the several proteins unique to the U12-type spliceosomes, an Arabidopsis thaliana AtU11/U12-31K protein has been shown to be indispensible for proper U12 intron splicing and for normal growth and development of Arabidopsis plants. Here, we assessed the functional roles of the rice (Oryza sativa) OsU11/U12-31K protein in U12 intron splicing and development of plants. The U11/U12-31K transcripts were abundantly expressed in the shoot apical meristems (SAMs) of Arabidopsis and rice. Ectopic expression of OsU11/U12-31K in AtU11/U12-31K-defecient Arabidopsis mutant complemented the incorrect U12 intron splicing and abnormal development phenotypes of the Arabidopsis mutant plants. Impaired cell division activity in the SAMs and inflorescence stems observed in the AtU11/U12-31K-deficient mutant was completely recovered to normal by the expression of OsU11/U12-31K. Similar to Arabidopsis AtU11/U12-31K, rice OsU11/U12-31K was determined to harbor RNA chaperone activity. Collectively, the present findings provide evidence for the emerging idea that the U11/U12-31K protein is an indispensible RNA chaperone that functions in U12 intron splicing and is necessary for normal development of monocotyledonous plants as well as dicotyledonous plants.

| S-EPMC3422263 | biostudies-literature

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