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The RNA hairpin binder TRIM71 modulates alternative splicing by repressing Mbnl1

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE130248 | GEO | 2019/08/01

REPOSITORIES: GEO

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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 [RNA-seq]

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

2019-08-01 | GSE130897 | 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

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

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 [RNA-seq & Ribo-seq]

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

| PRJNA541924 | ENA

TRIM71R595H/R595H mutations and TRIM71-KO in mESC lead to similar transcriptomic changes, which indicate a poised state toward neural differentiation

Project description:Mutations in TRIM71’s RNA-binding domain leads to congenital hydrocephalus in human patients and a TRIM71 mutant mouse model (Trim71R595H/+). Additionally, homozygous Trim71R595H/R595H mice phenocopy the neural tube defects and premature neural differentiation observed in TRIM71-KO mice. As RNA-Seq analyses revealed that TRIM71-KO mESC are poised for neural differentiation, we aimed to also examine the transcriptomes of TRIM71R595H/R595H and TRIM71R595H/+ mESC. Both TRIM71-KO and TRIM71R595H/R595H mutations in mESC result in transcriptomic changes with similar patterns, when compared to control mESC. Similar to TRIM71-KO, the transcriptome of Trim71R595H/R595H mESC indicates a poised state of mutated mESC towards neural differentiation.

2022-02-11 | GSE189420 | 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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