Staufen2 deficiency leads to impaired response to novelty in mice

Popper, Bastian; Demleitner, Antonia Franziska; Bolivar, Valerie J.; Kusek, Gretchen; Snyder-Keller, Abigail; Schieweck, Rico; Temple, Sally; Kiebler, Michael

doi:10.1016/j.nlm.2018.02.027

Cited by 16 publications

(22 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, in developing mouse cortex, STAU2 regulates the balance between neural stem cell maintenance and differentiation [21,22]: STAU2 downregulation induces cell differentiation while its overexpression produces periventricular neuronal masses. STAU2 depletion in mouse and rat brains inpairs hippocampal spatial working memory, spatial novelty detection and/or associative learning and memory [23,24]. This is consistent with the importance of STAU2 for dendritic spine morphogenesis and for long-term synaptic depression [13,15].…”

Section: Introductionsupporting

confidence: 78%

STAU2 Protein Level is Controlled by Caspases and the CHK1 Pathway and Regulates Cell Cycle Progression in the Non-transformed hTERT-RPE1 Cells

Condé

Beaujois

DesGroseillers

2020

Preprint

View full text Add to dashboard Cite

Background: Staufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from the STAU2 gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation. Results: CRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway dissociates STAU1 from proteins involved in translation and RNA metabolism. Conclusions: These results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. This novel function of STAU2 is regulated by caspases and by the kinase CHK1 pathway.

show abstract

Section: Introductionsupporting

confidence: 78%

STAU2 Protein Level is Controlled by Caspases and the CHK1 Pathway and Regulates Cell Cycle Progression in the Non-transformed hTERT-RPE1 Cells

Condé

Beaujois

DesGroseillers

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…For behavioral analysis, C57Bl6/JRj and CCR2 −/− (males, 2.5-3 months old) were housed in groups of 2-5 animals in standard Typ II long filter top cages (Tecniplast, Germany) under specific pathogen free conditions with a 12/12 hr light-dark cycle. Mice underwent a standardized 4-weeks behavior training starting at 24 hr after single or repetitive injury, and were exposed to a set of behavioral tests Open field test (OF) was performed as previously described (Popper et al, 2018). In brief, for habituation in the test environment, mice were placed in the center of a 80 × 40 cm acrylic OF box at 1 dpi and were allowed to freely investigate the testing environment for 4 min.…”

Section: Behavioral Testsmentioning

confidence: 99%

“…Barnes maze assay (BM) was performed using the Barnes maze platform adapted to mice (Barnes, 1979), as previously described (Popper et al, 2018). In brief, all mice were placed in the center of the The number of primary errors and the escape latency was determined during 240 s. The individual strategy to find the flight box (direct, wall, random) was analyzed by video tracking of all mice tested in the BM set up.…”

Section: Behavioral Testsmentioning

confidence: 99%

Repetitive injury and absence of monocytes promote astrocyte self‐renewal and neurological recovery

Canhos

Chen

Falk

et al. 2020

Glia

Self Cite

View full text Add to dashboard Cite

Unlike microglia and NG2 glia, astrocytes are incapable of migrating to sites of injury in the posttraumatic cerebral cortex, instead relying on proliferation to replenish their numbers and distribution in the affected region. However, neither the spectrum of their proliferative repertoire nor their postinjury distribution has been examined in vivo. Using a combination of different thymidine analogs and clonal analysis in a model of repetitive traumatic brain injury, we show for the first time that astrocytes that are quiescent following an initial injury can be coerced to proliferate after a repeated insult in the cerebral cortex grey matter. Interestingly, this process is promoted by invasion of monocytes to the injury site, as their genetic ablation (using CCR2 −/− mice) increased the number of repetitively dividing astrocytes at the expense of newly proliferating astrocytes in repeatedly injured parenchyma. These differences profoundly affected both the distribution of astrocytes and recovery period for posttraumatic behavior deficits suggesting key roles of astrocyte selfrenewal in brain repair after injury.

show abstract

“…Both Staufen1 and 2 are involved in the localisation of neurite-related mRNAs but are thought to have a nonredundant function. The reduced expression of the neuron-specific Staufen2, which we focus on, alters synaptic plasticity and memory [86,88], which is not surprising as the targets of these protein include CAM-KII mRNA.…”

Section: Staufen2mentioning

confidence: 95%

Joining the dots – protein‐RNA interactions mediating local mRNA translation in neurons

Gallagher

Ramos

2018

FEBS Letters

View full text Add to dashboard Cite

Establishing and maintaining the complex network of connections required for neuronal communication requires the transport and in situ translation of large groups of mRNAs to create local proteomes. In this Review, we discuss the regulation of local mRNA translation in neurons and the RNA-binding proteins that recognise RNA zipcode elements and connect the mRNAs to the cellular transport networks, as well as regulate their translation control. However, mRNA recognition by the regulatory proteins is mediated by the combinatorial action of multiple RNA-binding domains. This increases the specificity and affinity of the interaction, while allowing the protein to recognise a diverse set of targets and mediate a range of mechanisms for translational regulation. The structural and molecular understanding of the interactions can be used together with novel microscopy and transcriptome-wide data to build a mechanistic framework for the regulation of local mRNA translation.

show abstract

Staufen2 deficiency leads to impaired response to novelty in mice

Cited by 16 publications

References 40 publications

STAU2 Protein Level is Controlled by Caspases and the CHK1 Pathway and Regulates Cell Cycle Progression in the Non-transformed hTERT-RPE1 Cells

STAU2 Protein Level is Controlled by Caspases and the CHK1 Pathway and Regulates Cell Cycle Progression in the Non-transformed hTERT-RPE1 Cells

Repetitive injury and absence of monocytes promote astrocyte self‐renewal and neurological recovery

Joining the dots – protein‐RNA interactions mediating local mRNA translation in neurons

Contact Info

Product

Resources

About