Translating Messages in Different Neighborhoods

Chin, Ashley; Lécuyer, Éric

doi:10.1016/j.devcel.2020.09.006

Cited by 5 publications

(5 citation statements)

References 12 publications

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“…The authors propose that the translations of subunit complexes are spatially confined. These ideas are discussed in terms of compartmentalized translation principles with regulatory implications in development 56 , 57 . It would be fruitful to extend these concepts to describing the complex processes of granule formation in the germ plasm compartment of a mature oocyte where gNAC is localized accord to our preliminary experiments.…”

Section: Discussionmentioning

confidence: 99%

Extended disordered regions of ribosome-associated NAC proteins paralogs belong only to the germline in Drosophila melanogaster

Kogan

Mikhaleva

Olenkina

et al. 2022

Sci Rep

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The nascent polypeptide-associated complex (NAC) consisting of α- and β-subunits is an essential ribosome-associated protein conserved in eukaryotes. NAC is a ubiquitously expressed co-translational regulator of nascent protein folding and sorting providing for homeostasis of cellular proteins. Here we report on discovering the germline-specific NACαβ paralogs (gNACs), whose β-subunits, non-distinguishable by ordinary immunodetection, are encoded by five highly homologous gene copies, while the α-subunit is encoded by a single αNAC gene. The gNAC expression is detected in the primordial embryonic and adult gonads via immunostaining. The germline-specific α and β subunits differ from the ubiquitously expressed paralogs by the extended intrinsically disordered regions (IDRs) acquired at the N- and C-termini of the coding regions, predicted to be phosphorylated. The presence of distinct phosphorylated isoforms of gNAC-β subunits is confirmed by comparing of their profiles by 2D-isoeletrofocusing resolution before and after phosphatase treatment of testis ribosomes. We revealed that the predicted S/T sites of phosphorylation in the individual orthologous IDRs of gNAC-β sequences of Drosophila species are positionally conserved despite these disordered regions are drastically different. We propose the IDR-dependent molecular crowding and specific coordination of NAC and other proteostasis regulatory factors at the ribosomes of germinal cells. Our findings imply that there may be a functional crosstalk between the germinal and ubiquitous α- and β-subunits based on assessing their depletion effects on the fly viability and gonad development.

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Section: Discussionmentioning

confidence: 99%

Extended disordered regions of ribosome-associated NAC proteins paralogs belong only to the germline in Drosophila melanogaster

Kogan

Mikhaleva

Olenkina

et al. 2022

Sci Rep

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“…Interestingly, actin-rich deposits like Hirano bodies have also been observed in ALS and Alzheimer’s disease ( Rao and Cohen, 1990 ; Hirano, 1994 ; Gourlay and Ayscough, 2005 ). These aggregations may result from mRNA transport defects and a subsequently altered subcellular localization landscape and cellular stress ( Canclini et al, 2020 ; Chin and Lecuyer, 2020 ; Markmiller et al, 2021 ). In addition, nucleocytoplasmic transport defects might affect this tight regulation of the exchange of proteins and RNAs between cytoplasm and nucleus ( Giampetruzzi et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Age-dependent increase of cytoskeletal components in sensory axons in human skin

Metzner

Darawsha²,

Wang³

et al. 2022

Front. Cell Dev. Biol.

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Aging is a complex process characterized by several molecular and cellular imbalances. The composition and stability of the neuronal cytoskeleton is essential for the maintenance of homeostasis, especially in long neurites. Using human skin biopsies containing sensory axons from a cohort of healthy individuals, we investigate alterations in cytoskeletal content and sensory axon caliber during aging via quantitative immunostainings. Cytoskeletal components show an increase with aging in both sexes, while elevation in axon diameter is only evident in males. Transcriptomic data from aging males illustrate various patterns in gene expression during aging. Together, the data suggest gender-specific changes during aging in peripheral sensory axons, possibly influencing cytoskeletal functionality and axonal caliber. These changes may cumulatively increase susceptibility of aged individuals to neurodegenerative diseases.

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“…The authors propose that the translations of subunit complexes are spatially confined. These ideas are discussed in view of compartmentalized translation principles with regulatory implications in development [52]. It would be attractive to extend such concepts to the description the complex processes of granule formation in the germ plasm compartment of a mature oocyte that can be accompanied by the gNAC in D. melanogaster based on our preliminary experiments.…”

Section: Discussionmentioning

confidence: 99%

Detection of the germline specific NAC protein paralog enriched by intrinsically disordered regions inDrosophila melanogaster

Kogan

Mikhaleva

et al. 2021

Preprint

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Nascent polypeptide associated complex (NAC) consisting of α- and β-subunits is an essential conserved ubiquitously expressed ribosome-associated protein in eukaryotes. NAC is considered as a chaperone and co-translational regulator of nascent protein sorting providing homeostasis of cellular proteins. Here we discovered the germinal cell specific NAC (gNAC) homologue, which differs from the ubiquitously expressed NAC by the presence of expanded intrinsically disordered regions (IDRs) at the N- and C-ends of the α- and β-subunits, respectively. We propose this evolutionary acquisition of long IDRs drive gNAC to endow both the specific conformational plasticity for binding client proteins and novel functions regulated by post-transcriptional modifications (PTM). At the same time, we demonstrated that the well-known lethal effect of the loss of ubiquitous NAC-β is suppressed by ectopic expression of its germinal paralog indicating the absence of strict functional differences between the ubiquitous and germline NAC-β subunit paralogs for protein homeostasis.

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Translating Messages in Different Neighborhoods

Cited by 5 publications

References 12 publications

Extended disordered regions of ribosome-associated NAC proteins paralogs belong only to the germline in Drosophila melanogaster

Extended disordered regions of ribosome-associated NAC proteins paralogs belong only to the germline in Drosophila melanogaster

Age-dependent increase of cytoskeletal components in sensory axons in human skin

Detection of the germline specific NAC protein paralog enriched by intrinsically disordered regions inDrosophila melanogaster

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