The glycine arginine‐rich domain of the RNA‐binding protein nucleolin regulates its subcellular localization

Doron-Mandel, Ella; Koppel, Indrek; Abraham, Ofri; Rishal, Ida; Smith, Terika P.; Buchanan, Courtney N; Sahoo, Pabitra K.; Kadlec, Jan; Oses-Prieto, Juan; Kawaguchi, Riki; Alber, Stefanie; Zahavi, Eitan Erez; Matteo, Pierluigi Di; Pizio, Agostina Di; Song, Didi-Andreas; Okladnikov, Nataliya; Gordon, Dalia; Ben‐Dor, Shifra; Haffner-Krausz, Rebecca; Coppola, Giovanni; Burlingame, Alma L.; Jungwirth, Pavel; Twiss, Jeffery L.; Fainzilber, Mike

doi:10.15252/embj.2020107158

Cited by 36 publications

(24 citation statements)

References 78 publications

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“…We previously demonstrated that sensory neurons from Dync1h1 Loa mice are characterized by increased axon length, in accordance with predictions from a model of a length-sensing mechanism based on motor-dependent bidirectional transport and the localization and local translation of key mRNAs in axons (Doron-Mandel et al, 2021; Perry et al, 2016; Rishal et al, 2012). However, interpretation of those results was complicated by the fact that the Loa mutation is a single nucleotide change rather than a clear loss of function allele.…”

Section: Introductionsupporting

confidence: 81%

A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders

Pizio

Marvaldi

Birling

et al. 2022

Preprint

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Size homeostasis is one of the most fundamental aspects of biology and it is particularly important for large cells as neurons. We have previously proposed a motor-dependent length-sensing and growth-regulating mechanism wherein a partial reduction in the levels of microtubule motor proteins should lead to accelerated neuronal growth. This prediction was originally validated in sensory neurons heterozygous for the Loa point mutation in dynein heavy chain 1 (Dync1h1Loa). Here we describe a new mouse model with a conditional allele allowing deletion of exons 24-25 in Dync1h1. Homozygous Islet1-Cre deletion of Dync1h1 is embryonic lethal, but heterozygous animals (Isl1-Dync1h1+/-) survive to adulthood with approximately 50% dynein expression in targeted cell types. Isl1-Dync1h1+/- adult sensory neurons reveal an accelerated growth phenotype, similar to that previously reported in Dync1h1Loa neurons. Moreover, Isl1-Dync1h1+/- mice show mild impairments in gait, proprioception and tactile sensation; and slightly impaired recovery from peripheral nerve injury. Thus, conditional deletion of Dync1h1 exons 24-25 enables targeted studies of the role of dynein in neuronal growth and neurological disorders.

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Section: Introductionsupporting

confidence: 81%

A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders

Pizio

Marvaldi

Birling

et al. 2022

Preprint

Self Cite

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“…Nucleolin mRNA was confirmed as a bona fide target that relies on these players; it encodes an RBP that regulates ribosome biogenesis but also localizes to distal neurites (Abdelmohsen et al, 2011; Perry et al, 2016). Ncl protein retrogradely transports importin β1 mRNA back to the soma to control cell size and associates with Kif5a through its glycine/arginine-rich domain (Doron-Mandel et al, 2021; Perry et al, 2016). Here, we find that Ncl mRNA itself is localized by MBNL and Kif1bα/Kif1c, raising the possibility that Ncl protein in neurites may arise via local translation.…”

Section: Discussionmentioning

confidence: 99%

Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes

Hildebrandt

Moss

Janusz-Kaminska

et al. 2022

Preprint

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RNA transport and local translation provide spatial control of gene expression, and RNA binding proteins (RBPs) act as critical adapters in this multi-step process. Muscleblind-like (MBNL) RNA binding proteins, implicated in myotonic dystrophy and cancer, localize RNAs to myoblast membranes and distal neurites through unknown mechanisms. We found that MBNL forms motile and anchored granules in neurons and myoblasts, and selectively associates with kinesins Kif1bα ; and Kif1c through its zinc finger (ZnF) domains. Other RBPs with similar ZnFs also associate with these kinesins, implicating a motor-RBP specificity code. Live cell imaging and fractionation revealed that membrane anchoring is mediated through the unstructured carboxy-terminal tail of MBNL1. Both kinesin- and membrane-recruitment functions were reconstituted using MBNL-MS2 coat protein fusions. This approach, termed RBP Module Recruitment and Imaging (RBP-MRI), decouples RNA binding, kinesin recruitment, and membrane anchoring functions, while also establishing general strategies for studying multi-functional, modular domains of RBPs.

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“…( D ) List of RBP domains associated with disease and dysfunction. Common diseases and abnormalities are included [ 249 , 250 , 251 , 252 , 253 , 254 ].…”

Section: Figurementioning

confidence: 99%

Emerging Roles of RNA-Binding Proteins in Neurodevelopment

Parra

Johnston

2022

JDB

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Diverse cell types in the central nervous system (CNS) are generated by a relatively small pool of neural stem cells during early development. Spatial and temporal regulation of stem cell behavior relies on precise coordination of gene expression. Well-studied mechanisms include hormone signaling, transcription factor activity, and chromatin remodeling processes. Much less is known about downstream RNA-dependent mechanisms including posttranscriptional regulation, nuclear export, alternative splicing, and transcript stability. These important functions are carried out by RNA-binding proteins (RBPs). Recent work has begun to explore how RBPs contribute to stem cell function and homeostasis, including their role in metabolism, transport, epigenetic regulation, and turnover of target transcripts. Additional layers of complexity are provided by the different target recognition mechanisms of each RBP as well as the posttranslational modifications of the RBPs themselves that alter function. Altogether, these functions allow RBPs to influence various aspects of RNA metabolism to regulate numerous cellular processes. Here we compile advances in RNA biology that have added to our still limited understanding of the role of RBPs in neurodevelopment.

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The glycine arginine‐rich domain of the RNA‐binding protein nucleolin regulates its subcellular localization

Cited by 36 publications

References 78 publications

A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders

A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders

Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes

Emerging Roles of RNA-Binding Proteins in Neurodevelopment

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