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The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1 [RNA-seq]

ABSTRACT: We demonstrate that TRIM71 alters stem cell splicing patterns through modulation of MBNL1 levels.

ORGANISM(S): Mus musculus

PROVIDER: GSE130897 | GEO | 2019/08/01

REPOSITORIES: GEO

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The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1

Project description:We demonstrate that global effects of TRIM71 on the cellular transcriptome of mouse embryonic stem cells (mESCs) are largely attributable to its RNA binding activity, and map the transcriptome-wide targets of wild-type TRIM71, NHL domain mutant TRIM71, and RING domain mutant TRIM71.

2019-08-01 | GSE130248 | GEO

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1.

Project description:TRIM71/LIN-41, a phylogenetically conserved regulator of development, controls stem cell fates. Mammalian TRIM71 exhibits both RNA-binding and protein ubiquitylation activities, but the functional contribution of either activity and relevant primary targets remain poorly understood. Here, we demonstrate that TRIM71 shapes the transcriptome of mouse embryonic stem cells (mESCs) predominantly through its RNA-binding activity. We reveal that TRIM71 binds targets through 3' untranslated region (UTR) hairpin motifs and that it acts predominantly by target degradation. TRIM71 mutations implicated in etiogenesis of human congenital hydrocephalus impair target silencing. We identify a set of primary targets consistently regulated in various human and mouse cell lines, including MBNL1 (Muscleblind-like protein 1). MBNL1 promotes cell differentiation through regulation of alternative splicing, and we demonstrate that TRIM71 promotes embryonic splicing patterns through MBNL1 repression. Hence, repression of MBNL1-dependent alternative splicing may contribute to TRIM71's function in regulating stem cell fates.

| S-EPMC6719626 | biostudies-literature

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1 [RNA-seq & Ribo-seq]

Project description:We demonstrate that global effects of TRIM71 on the cellular transcriptome of mouse embryonic stem cells (mESCs) are largely attributable to its RNA binding activity. We observe that target repression by TRIM71 in mESCs occurs predominantly through transcript degradation. We identify a core set of targets consistently regulated by TRIM71 in different human and mouse cell lines.

2019-08-01 | GSE130898 | GEO

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1

Project description:The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1

| PRJNA534452 | ENA

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1

Project description:The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1

| PRJNA554208 | ENA

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1 [RNA-seq]

Project description:The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1 [RNA-seq]

| PRJNA541923 | ENA

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-08-01 | GSE134125 | GEO

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1 [RNA-seq & Ribo-seq]

Project description:The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1 [RNA-seq & Ribo-seq]

| PRJNA541924 | ENA

MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia

Project description:In this study, we identify MBNL1 as a unique molecular vulnerability across MLL-rearranged leukemias. Through transcriptomic profiling and novel splicing analyses of MLL-rearranged leukemia cell lines following shRNA knockdown of MBNL1, we show that MBNL1 regulates alternative splicing (predominantly intron retention) of genes essential to MLL-rearranged leukemogenesis, such as DOT1L and SETD1A.

2020-03-25 | GSE123441 | GEO

mRNA sequencing of Trim71 conditional ("WT") and Trim71 KO mES cells

Project description:We report that Trim71 mutation does not lead to significant changes within the core regulatory network of mES cells, however, there is an upregulation of specific genes involved in neural differentiation. We thus conclude that Trim71 KO mES cells are poised for differentiation.

2015-10-01 | GSE62398 | GEO

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