De-centralizing the Central Dogma: mRNA translation in space and time

Bourke, Ashley M.; Schwarz, Andre; Schuman, Erin M.

doi:10.1016/j.molcel.2022.12.030

Cited by 31 publications

(20 citation statements)

References 249 publications

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“…Considering the cellular contexts that may preferentially allow mono-ribosomes to drive protein synthesis 89 , the stoichiometry of ribosomes on a transcript may be linked to the function of the cell. The Ribo-Calibration should help to unveil such a connection between the mode of ribosome stoichiometry and phenotype.…”

Section: Discussionmentioning

confidence: 99%

Absolute calibration of ribosome profiling assesses the dynamics of ribosomal flux on transcripts

Tomuro,

Mito,

Toh

et al. 2023

Preprint

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Ribosome profiling, which is based on deep sequencing of ribosome footprints, has served as a powerful tool to unveil the regulatory mechanism of protein synthesis. However, the current method has substantial issues: contamination by rRNAs and the lack of appropriate means to determine overall ribosome numbers in transcripts. Here, we overcome these hurdles through the development of "Ribo-FilterOut", which is based on the separation of footprints from ribosome subunits by ultrafiltration, and "Ribo-Calibration", which relies on external spike-ins of stoichiometry-defined mRNA-ribosome complexes. A combination of these approaches measures the absolute numbers of ribosomes on transcripts, the translation initiation rate, and the numbers of translation events on a transcript before its decay, all in a genome-wide manner. Moreover, our method revealed the allocations of ribosomes under heat shock stress, during aging, and across cell types. Our strategy transforms the ribosome profiling technique from relative to absolute quantification of translation.

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Section: Discussionmentioning

confidence: 99%

Absolute calibration of ribosome profiling assesses the dynamics of ribosomal flux on transcripts

Tomuro,

Mito,

Toh

et al. 2023

Preprint

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“…Textbook knowledge of the central dogma primarily focuses on protein expression in the cell body. , However, over 90% of a neuron’s proteins localize and function outside the cell body within synapses, dendrites, and axons . In addition, there exists a constant turnover demand of ∼10 6 new protein copies per minute per neuron .…”

Section: Investigating Cell Biological Processes Within Synapsesmentioning

confidence: 99%

Single-Molecule-Resolution Approaches in Synaptic Biology

Sun

2024

J. Phys. Chem. B

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Synapses between neurons are the primary loci for information transfer and storage in the brain. An individual neuron, alone, can make over 10000 synaptic contacts. It is, however, not easy to investigate what goes on locally within a synapse because many synaptic compartments are only a few hundred nanometers wide in size�close to the diffraction limit of light. To observe the biomolecular machinery and processes within synapses, in situ singlemolecule techniques are emerging as powerful tools. Guided by important biological questions, this Perspective will highlight recent advances in using these techniques to obtain in situ measurements of synaptic molecules in three aspects: the cell-biological machinery within synapses, the synaptic architecture, and the synaptic neurotransmitter receptors. These advances showcase the increasing importance of single-molecule-resolution techniques for accessing subcellular biophysical and biomolecular information related to the brain.

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“…RNPs have yet to be systematically analysed in lymphocytes and the majority of studies of translational regulation have focussed on individual RBPs. There is ample evidence that in neuronal tissues mRNAs can be transported in a repressed state to distal sites to be translated 33 . The proteins that mediate these processes, such as Fragile X Mental Retardation Protein (FMRP) and its paralogs are expressed by immune cells where they may be important for the specialised polarised functions of immune cells such as phagocytosis 34 and migration 35 in addition to regulating cytokines such as TNF 36,37 .…”

Section: Candidate Mechanisms To Dynamically Regulate Poised Mrnasmentioning

confidence: 99%

“…There is ample evidence that in neuronal tissues mRNAs can be transported in a repressed state to distal sites to be translated. 33 The proteins that mediate these processes, such as Fragile X Mental Retardation Protein (FMRP) and its paralogs are expressed by immune cells where they may be important for the specialised polarised functions of immune cells such as phagocytosis 34 and migration 35 in addition to regulating cytokines such as TNF. 36,37 FMRP-mediated translation repression is promoted by phosphorylation, 38 trans-acting regulators of the location and persistence of mRNA.…”

Section: Candidate Mechanisms To Dynamically Regulate Poised Mrnasmentioning

confidence: 99%

Regulation and function of poised mRNAs in lymphocytes

Turner

2023

BioEssays

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Pre-existing but untranslated or 'poised' mRNA exists as a means to rapidly induce the production of specific proteins in response to stimuli and as a safeguard to limit the actions of these proteins. The translation of poised mRNA enables immune cells to express quickly genes that enhance immune responses. The molecular mechanisms that repress the translation of poised mRNA and, upon stimulation, enable translation have yet to be elucidated. They likely reflect intrinsic properties of the mRNAs and their interactions with trans-acting factors that direct poised mRNAs away from or into the ribosome. Here, I discuss mechanisms by which this might be regulated.

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De-centralizing the Central Dogma: mRNA translation in space and time

Cited by 31 publications

References 249 publications

Absolute calibration of ribosome profiling assesses the dynamics of ribosomal flux on transcripts

Absolute calibration of ribosome profiling assesses the dynamics of ribosomal flux on transcripts

Single-Molecule-Resolution Approaches in Synaptic Biology

Regulation and function of poised mRNAs in lymphocytes

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