Translational Control during Developmental Transitions

Teixeira, Felipe Karam; Lehmann, Ruth

doi:10.1101/cshperspect.a032987

Cited by 69 publications

(60 citation statements)

References 147 publications

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“…Translational regulation in stem cells has emerged as an important new area of study, especially given the low transcriptional activity of these cells in embryonic and hematopoietic systems (see Teixeira and Lehmann 2018). Thus, the 4E-BPs are required to limit translation and ensure the maintenance of hematopoietic and embryonic stem cells (Signer et al 2016;Tahmasebi et al 2016), whereas eIF2α phosphorylation promotes the maintenance of muscle stem cells (Zismanov et al 2016).…”

Section: Considering Heterogeneous Cell Populations In Tumors Cancer mentioning

confidence: 99%

Translational Control in Cancer

Robichaud

Sonenberg

Ruggero

et al. 2018

Cold Spring Harb Perspect Biol

205

172

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The translation of messenger RNAs (mRNAs) into proteins is a key event in the regulation of gene expression. This is especially true in the cancer setting, as many oncogenes and transforming events are regulated at this level. Cancer-promoting factors that are translationally regulated include cyclins, antiapoptotic factors, proangiogenic factors, regulators of cell metabolism, prometastatic factors, immune modulators, and proteins involved in DNA repair. This review discusses the diverse means by which cancer cells deregulate and reprogram translation, and the resulting oncogenic impacts, providing insights into the complexity of translational control in cancer and its targeting for cancer therapy.

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Section: Considering Heterogeneous Cell Populations In Tumors Cancer mentioning

confidence: 99%

Translational Control in Cancer

Robichaud

Sonenberg

Ruggero

et al. 2018

Cold Spring Harb Perspect Biol

205

172

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“…Although transcription is considered the main predictor of protein levels under steady state conditions, posttranscriptional control has been shown to play a dominant role during short-term state transitions such as differentiation [22,24,25]. The ability to change mRNA "translation on demand" allows proteins to be rapidly available in response to extrinsic stimuli and cellular changes [22].…”

Section: Going Beyond Transcriptional and Epigenetic Mechanisms: Postmentioning

confidence: 99%

“…Low protein synthesis is a general feature of the stem cell state in embryonic, hematopoietic, hair follicle, muscle, and neural stem cells [25]. In these cells, inhibition of protein synthesis tends to increase self-renewal while activation of protein synthesis promotes the onset of differentiation [25].…”

Section: Global Control Of Protein Translationmentioning

confidence: 99%

Translating neural stem cells to neurons in the mammalian brain

2019

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The mammalian neocortex underlies our perception of sensory information, performance of motor activities, and higherorder cognition. During mammalian embryogenesis, radial glial precursor cells sequentially give rise to diverse populations of excitatory cortical neurons, followed by astrocytes and oligodendrocytes. A subpopulation of these embryonic neural precursors persists into adulthood as neural stem cells, which give rise to inhibitory interneurons and glia. Although the intrinsic mechanisms instructing the genesis of these distinct progeny have been well-studied, most work to date has focused on transcriptional, epigenetic, and cell-cycle control. Recent studies, however, have shown that posttranscriptional mechanisms also regulate the cell fate choices of transcriptionally primed neural precursors during cortical development. These mechanisms are mediated primarily by RNA-binding proteins and microRNAs that coordinately regulate mRNA translation, stability, splicing, and localization. Together, these findings point to an extensive network of posttranscriptional control and provide insight into both normal cortical development and disease. They also add another layer of complexity to brain development and raise important biological questions for future investigation. Facts • Numerous posttranscriptional regulators including RBPs and miRNAs are expressed in a temporally dynamic and cell-type specific manner during embryonic corticogenesis. • Posttranscriptional mechanisms control cell fate decisions of embryonic and adult neural precursor cells. How do RBPs and miRNAs contribute to neurodevelopmental and neurological disorders?

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“…Translational regulation plays a particularly important role during early embryonic development; during the time window of near complete shutdown of transcription after fertilization, mRNA translation serves as the main layer of gene regulation by which the maternally stored mRNAs are translated in a highly spatiotemporally-controlled manner 11 . Furthermore, maintenance of the undifferentiated status in both adult and embryonic stem cells (ESCs) is associated with low mRNA translation rates and restricted protein synthesis [12][13][14][15] .…”

mentioning

confidence: 99%

The translational landscape of ground state pluripotency

et al. 2020

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Translational control plays a central role in regulation of gene expression and can lead to significant divergence between mRNA-and protein-abundance. Here, we used genome-wide approaches combined with time-course analysis to measure the mRNA-abundance, mRNAtranslation rate and protein expression during the transition of naïve-to-primed mouse embryonic stem cells (ESCs). We find that the ground state ESCs cultured with GSK3-, MEKinhibitors and LIF (2iL) display higher ribosome density on a selective set of mRNAs. This set of mRNAs undergo strong translational buffering to maintain stable protein expression levels in 2iL-ESCs. Importantly, we show that the global alteration of cellular proteome during the transition of naïve-to-primed pluripotency is largely accompanied by transcriptional rewiring. Thus, we provide a comprehensive and detailed overview of the global changes in gene expression in different states of ESCs and dissect the relative contributions of mRNAtranscription, translation and regulation of protein stability in controlling protein abundance.

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Translational Control during Developmental Transitions

Cited by 69 publications

References 147 publications

Translational Control in Cancer

Translational Control in Cancer

Translating neural stem cells to neurons in the mammalian brain

The translational landscape of ground state pluripotency

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