Tagged actin mRNA dysregulation in IGF2BP1−/− mice

Núñez, Leti; Buxbaum, Adina R.; Katz, Zachary; Lopez-Jones, Melissa; Nwokafor, Chiso; Czaplinski, Kevin; Pan, Feng; Rosenberg, Jason; Monday, Hannah R.; Singer, Robert H.

doi:10.1073/pnas.2208465119

Cited by 15 publications

(7 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6A-I). The FB phenotype is reminiscent of cortical layer deformations observed in Imp1 knock-out mice 85 .…”

Section: Imp Regulates CX Neuropil Morphology and Neuropeptide Distri...mentioning

confidence: 94%

The RNA-binding protein, Imp specifies olfactory navigation circuitry and behavior inDrosophila

Hamid,

Gattuso,

Caglar

et al. 2023

Preprint

View full text Add to dashboard Cite

Complex behaviors depend on the precise developmental specification of neuronal circuits, but the relationship between genetic programs for neural development, circuit structure, and behavioral output is often unclear. The central complex (CX) is a conserved sensory-motor integration center in insects that governs many higher-order behaviors and largely derives from a small number of Type II neural stem cells. Here, we show that Imp, a conserved IGF-II mRNA-binding protein expressed in Type II neural stem cells, specifies components of CX olfactory navigation circuitry. We show: (1) that multiple components of olfactory navigation circuitry arise from Type II neural stem cells and manipulating Imp expression in Type II neural stem cells alters the number and morphology of many of these circuit elements, with the most potent effects on neurons targeting the ventral layers of the fan-shaped body. (2) Imp regulates the specification of Tachykinin expressing ventral fan-shaped body input neurons. (3) Imp in Type II neural stem cells alters the morphology of the CX neuropil structures. (4) Loss of Imp in Type II neural stem cells abolishes upwind orientation to attractive odor while leaving locomotion and odor-evoked regulation of movement intact. Taken together, our work establishes that a single temporally expressed gene can regulate the expression of a complex behavior through the developmental specification of multiple circuit components and provides a first step towards a developmental dissection of the CX and its roles in behavior.

show abstract

“…6A-I). The FB phenotype is reminiscent of cortical layer deformations observed in Imp1 knock-out mice 85 .…”

Section: Imp Regulates CX Neuropil Morphology and Neuropeptide Distri...mentioning

confidence: 94%

The RNA-binding protein, Imp specifies olfactory navigation circuitry and behavior inDrosophila

Hamid,

Gattuso,

Caglar

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Both features have been reported in MDS mouse models 26,33 . IGF2BP1 (OMIM*608288) is upregulated is involved in growth cone migration, dendritic branching and synapse formation in neurons, and also transports transcripts required for axonal regeneration on adult sensory neurons 34 . Altogether, our data emphasise a disruption in vesicle formation, cargo uptake and secretion.…”

Section: Vesicular Transportmentioning

confidence: 99%

Multi-omics in MECP2 duplication syndrome patients and carriers.

Pascual-Alonso,

Xiol,

Smirnov

et al. 2024

Preprint

View full text Add to dashboard Cite

MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by the gain of dose of at least the genes MECP2 and IRAK1 and is characterised by intellectual disability (ID), developmental delay, hypotonia, epilepsy and recurrent infections. It mainly affects males, and females can be affected or asymptomatic carriers. Rett syndrome (RTT) is mainly triggered by loss of function mutations in MECP2 and is a well described syndrome that presents ID, epilepsy, lack of purposeful hand use and impaired speech, among others. As a result of implementing omics technology, altered biological pathways in human RTT samples have been reported, but such molecular characterisation has not been performed in MDS patients. We gathered human skin fibroblasts from 17 patients with MDS, 10 MECP2 duplication carrier mothers and 21 RTT patients, and performed multi-omics (RNAseq and proteomics) analysis. Here, we provide a thorough description and compare the shared and specific dysregulated biological processes between the cohorts. We also highlight the genes TMOD2, SRGAP1, COPS2, CNPY2, IGF2BP1, MOB2, VASP, FZD7, ECSIT andKIF3B as biomarker and therapeutic target candidates due to their implication in neuronal functions. Defining the RNA and protein profiles has shown that our four cohorts are less alike than expected by their shared phenotypes.

show abstract

“…Unbound ZBP1 is involved in the induction of apoptosis but, when included in the GAP-43/β-actin complex, it is not, and neurite growth is allowed. The release of the mRNAs from the complex formed with ZBP1 is determined by specific axonal or dendritic extension signals that activate SRC kinase, which, in turn, phosphorylates ZBP1 [ 185 , 208 ]. Interestingly, β1-importin, a protein normally involved in nuclear import, has been recently described as a possible RBP because of its presence in neurites and its interaction with the Neuritin 1 (Nrn1) mRNA, encoding a protein which participates in neurite outgrowth [ 209 ].…”

Section: Post-transcriptional Regulation Of Gene Expression In the Ne...mentioning

confidence: 99%

RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration

Schiera

Schirò

Liegro

2022

IJMS

View full text Add to dashboard Cite

A central aspect of nervous system development and function is the post-transcriptional regulation of mRNA fate, which implies time- and site-dependent translation, in response to cues originating from cell-to-cell crosstalk. Such events are fundamental for the establishment of brain cell asymmetry, as well as of long-lasting modifications of synapses (long-term potentiation: LTP), responsible for learning, memory, and higher cognitive functions. Post-transcriptional regulation is in turn dependent on RNA-binding proteins that, by recognizing and binding brief RNA sequences, base modifications, or secondary/tertiary structures, are able to control maturation, localization, stability, and translation of the transcripts. Notably, most RBPs contain intrinsically disordered regions (IDRs) that are thought to be involved in the formation of membrane-less structures, probably due to liquid–liquid phase separation (LLPS). Such structures are evidenced as a variety of granules that contain proteins and different classes of RNAs. The other side of the peculiar properties of IDRs is, however, that, under altered cellular conditions, they are also prone to form aggregates, as observed in neurodegeneration. Interestingly, RBPs, as part of both normal and aggregated complexes, are also able to enter extracellular vesicles (EVs), and in doing so, they can also reach cells other than those that produced them.

show abstract

Tagged actin mRNA dysregulation in IGF2BP1−/− mice

Cited by 15 publications

References 58 publications

The RNA-binding protein, Imp specifies olfactory navigation circuitry and behavior inDrosophila

The RNA-binding protein, Imp specifies olfactory navigation circuitry and behavior inDrosophila

Multi-omics in MECP2 duplication syndrome patients and carriers.

RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration

Contact Info

Product

Resources

About