Translation of Human β-Actin mRNA is Regulated by mTOR Pathway

Eliseeva, Irina A.; Vasilieva, Maria; Ovchinnikov, Lev P.

doi:10.3390/genes10020096

Cited by 16 publications

(16 citation statements)

References 57 publications

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“…Instead, it is possible that mTORC1 controls translation initiation and local mRNA transport ( Pilaz et al, 2016 ; Pilaz and Silver, 2017 ) into the basal processes of oRG cells. Recent studies have identified direct regulation of translation of the human ß-Actin mRNA by mTORC1 and shown that this regulation may be cell-type dependent ( Eliseeva et al, 2019 ). mTORC1 may therefore, indirectly affect the ability of oRGs to generate cytoskeletal proteins needed for basal process elongation and maintenance by regulating protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…mTORC1 and C2 act in large multi-protein complexes to control both aspects of protein regulation. As a result, optimum levels of individual proteins are needed for the proper assembly of functional complexes ( Ardestani et al, 2018 ; Eliseeva et al, 2019 ; Varusai and Nguyen, 2018 ). It is probable that too much or too little of any of the individual proteins will result in abnormal functional protein assemblies and disrupted cytoskeleton in oRG cells.…”

Section: Discussionmentioning

confidence: 99%

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mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

Andrews

Subramanian

Kriegstein

2020

eLife

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Outer radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development. We find that dysregulation of mTOR signaling specifically affects oRG cells, but not other progenitor types, by changing the actin cytoskeleton through the activity of the Rho-GTPase, CDC42. These effects change oRG cellular morphology, migration, and mitotic behavior, but do not affect proliferation or cell fate. Thus, mTOR signaling can regulate the architecture of the developing human cortex by maintaining the cytoskeletal organization of oRG cells and the radial glia scaffold. Our study provides insight into how mTOR dysregulation may contribute to neurodevelopmental disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

Andrews

Subramanian

Kriegstein

2020

eLife

View full text Add to dashboard Cite

show abstract

“…Instead, it is possible that mTORC1 controls translation initiation and local mRNA transport (Pilaz et al, 2016;Pilaz & Silver, 2017) into the basal processes of oRG cells. Recent studies have identified direct regulation of translation of the human ß-Actin mRNA by mTORC1 and shown that this regulation may be cell-type dependent (Eliseeva et al, 2019). mTORC1 may therefore, indirectly affect the ability of oRGs to generate cytoskeletal proteins needed for basal process elongation and maintenance by regulating protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…mTORC1 and C2 act in large multi-protein complexes to control both aspects of protein regulation. As a result, optimum levels of individual proteins are needed for the proper assembly of functional complexes (Ardestani et al, 2018;Eliseeva et al, 2019;Varusai & Nguyen, 2018). It is probable that too much or too little of any of the individual proteins will result in abnormal functional protein assemblies and disrupted cytoskeleton in oRG cells.…”

Section: Discussionmentioning

confidence: 99%

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

Andrews

Subramanian

Kriegstein

2020

Preprint

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Outer radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development. We find that dysregulation of mTOR signaling specifically affects oRG cells, but not other progenitor types, by changing the actin cytoskeleton through the activity of the GTPase, CDC42. These effects change oRG cellular morphology, migration, and mitotic behavior. Thus, mTOR signaling can regulate the architecture of the developing human cortex by maintaining the cytoskeletal organization of oRG cells and the radial glia scaffold. Our study provides insight into how mTOR dysregulation may contribute to neurodevelopmental disease.

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“…Plasmids pSpCas9(BB)-2A-Puro (a gift from Feng Zhang; Addgene plasmid #48,139) [45], pcDNA3-HA-YB-1 and pcDNA3-HA [5], pGFP-c3 [46], pNL2.2 SLU7-NlucP [47], pSP36TLuc-A50 [48], pcDNA-3.1-puro (kindly provided by Dr. Dmitriev, A.N. Belozersky Institute of Physico-Chemical Biology, MSU).…”

Section: Methodsmentioning

confidence: 99%

YB-3 substitutes YB-1 in global mRNA binding

et al. 2020

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Y-box binding proteins are DNA-and RNA-binding proteins with an evolutionarily ancient and conserved cold shock domain. The Y-box binding protein 1 (YB-1) is the most studied due to its abundance in somatic cells. YB-1 is involved in a variety of cellular processes, including proliferation, differentiation and stress response. Here, using Ribo-Seq and RIP-Seq we confirm that YB-1 binds a wide range of mRNAs and globally acts as a translation inhibitor. Surprisingly, YBX1 knockout results in only minor alterations in the expression of other genes, mostly caused by changes in RNA abundance. But YB-3 mRNA is an exception: it is better translated in the absence of YB-1, thereby producing an increased amount of YB-3 and thus suggesting that its synthesis is under YB-1 negative control. We have shown that the set of mRNAs bound to YB-3 is strikingly similar to that of YB-1, and that the mRNA-binding by YB-3 is enhanced in the absence of YB-1, resulting in a similar global reduction of translation of bound mRNAs in YB-1-null cells. Thus, YB-3 acts as a substitute for YB-1 in mRNA binding and, probably, in global translational control. ARTICLE HISTORY

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Translation of Human β-Actin mRNA is Regulated by mTOR Pathway

Cited by 16 publications

References 57 publications

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

YB-3 substitutes YB-1 in global mRNA binding

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