RNA export through the nuclear pore complex is directional

Ashkenazy-Titelman, Asaf; Atrash, Mohammad K; Boocholez, Alon; Kinor, Noa; Shav‐Tal, Yaron

doi:10.1038/s41467-022-33572-7

Cited by 22 publications

(13 citation statements)

References 56 publications

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“…Notably, in cytoplasmic extract, the nanobody could bind GFP-EIF4A3 also in the heavy gradient fractions (Extended Data Fig. 10d), in agreement with a lower degree of compaction in cytoplasmic compared to nuclear mRNPs and the absence of TREX in the cytoplasm 15,16 . Further, we observed that all endogenously tagged GFP-THOC5 or lentiviral overexpressed THOC1-GFP could be immunoprecipitated using anti-GFP nanobody beads from the respective nuclear extracts (Extended Data Fig.…”

Section: Mrnps Form Compact Globulessupporting

confidence: 63%

mRNA recognition and packaging by the human transcription–export complex

Pacheco-Fiallos

Vorländer

Riabov-Bassat

et al. 2023

Nature

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Newly made messenger RNAs are processed and packaged into ribonucleoprotein complexes (mRNPs) and recognized by the essential transcription-export complex (TREX) for nuclear export 1,2 . However, the mechanisms of mRNP recognition and three-dimensional organization are poorly understood 3 . Here, we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the two-megadalton TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon-junction complexes. Exon-junction complexes can multimerize through ALYREF, suggesting a mechanism for mRNP organization. Endogenous mRNPs form compact 'globules' that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact, and protect mRNAs to promote their packaging for nuclear export. The mRNP globule organization provides a framework to understand how mRNP architecture could facilitate mRNA biogenesis and export. This work is licensed under a CC BY 4.0 International license.

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Section: Mrnps Form Compact Globulessupporting

confidence: 63%

mRNA recognition and packaging by the human transcription–export complex

Pacheco-Fiallos

Vorländer

Riabov-Bassat

et al. 2023

Nature

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“…Our dissipative particle dynamics (DPD) model has qualitatively recapitulated the experimental results from living cells that mechanomemory persists in the chromatin, and nucleoplasm diffusivity for tens of minutes after stress cessation and this memory is regulated by the NPCs. Recent reports show that the size of and the transport via the NPCs that is tethered to the cytoskeleton is regulated by the tension in the nuclear envelope ( 21 , 27 ), and transport of RNA via NPCs is unidirectional ( 28 ). Our current finding that the mechanomemory of chromatin diffusivity and nucleoplasm protein diffusivity extends the current understanding of the role of the NPCs and highlights the importance of the molecular exchange between the nucleus and the cytoplasm in regulating external force-induced nuclear activities and functions.…”

Section: Discussionmentioning

confidence: 99%

Mechanomemory in protein diffusivity of chromatin and nucleoplasm after force cessation

Rashid

Liu

Wang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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It is known that external mechanical forces can regulate structures and functions of living cells and tissues in physiology and diseases. However, after cessation of the force, how structures are altered in response to the dynamics of the chromatin and molecules in the nucleoplasm remains elusive. Here, using single-molecule imaging approaches, we show that exogenous local forces via integrins applied for 2 to 10 min decondensed the chromatin and increased chromatin and nucleoplasm protein mobility inside the nucleus, leading to elevated diffusivity of single protein molecules in the nucleoplasm, tens of minutes after the cessation of force. Diffusion experiments with fluorescence correlation spectroscopy in live single cells show that the mechanomemory in chromatin and nucleoplasm protein diffusivity was regulated by nuclear pore complexes. Protein molecular dynamics simulation recapitulated the experimental findings in live cells and showed that nucleoplasm protein diffusivity was regulated by the number of nuclear pore complexes. The mechanomemory in elevated protein diffusivity of the nucleoplasm after force cessation represents a physical process that reverses protein–protein condensation in phase separation via unjamming of the chromatin. Our findings of mechanomemory in chromatin and nucleoplasm protein diffusivity suggest that the effect of force on the nucleus remains tens of minutes after force cessation and thus is more far-reaching than previously anticipated.

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“…Interestingly, although this process is ATP dependent in opisthokonts [67], the lack of many ATPases in the nuclear pore complex of trypanosomatids suggests that mRNA nuclear export is GTP driven in these organisms [68,69]. Assuming that the amount of HEBs (high-energy bonds) consumed by T. brucei for RNA nuclear export is the same as that consumed by yeast (i.e., 2 ATP molecules per transcript) [70,71] we can estimate a cost for the export of the total number of rRNAs (those for maintenance and those for duplication) minus the SL-RNAs, which remain in the nucleus. The total HEB equivalent to ATP used for this process is 3.1 x 10 5 for rRNAs, 4.0 x 10 3 for VSG mRNAs and 7.6 x 10 4 for all other mRNAs.…”

Section: Plos Pathogensmentioning

confidence: 99%

How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell

et al. 2023

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ATP hydrolysis is required for the synthesis, transport and polymerization of monomers for macromolecules as well as for the assembly of the latter into cellular structures. Other cellular processes not directly related to synthesis of biomass, such as maintenance of membrane potential and cellular shape, also require ATP. The unicellular flagellated parasite Trypanosoma brucei has a complex digenetic life cycle. The primary energy source for this parasite in its bloodstream form (BSF) is glucose, which is abundant in the host’s bloodstream. Here, we made a detailed estimation of the energy budget during the BSF cell cycle. As glycolysis is the source of most produced ATP, we calculated that a single parasite produces 6.0 x 1011 molecules of ATP/cell cycle. Total biomass production (which involves biomass maintenance and duplication) accounts for ~63% of the total energy budget, while the total biomass duplication accounts for the remaining ~37% of the ATP consumption, with in both cases translation being the most expensive process. These values allowed us to estimate a theoretical YATP of 10.1 (g biomass)/mole ATP and a theoretical YATPmax of 28.6 (g biomass)/mole ATP. Flagellar motility, variant surface glycoprotein recycling, transport and maintenance of transmembrane potential account for less than 30% of the consumed ATP. Finally, there is still ~5.5% available in the budget that is being used for other cellular processes of as yet unknown cost. These data put a new perspective on the assumptions about the relative energetic weight of the processes a BSF trypanosome undergoes during its cell cycle.

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RNA export through the nuclear pore complex is directional

Cited by 22 publications

References 56 publications

mRNA recognition and packaging by the human transcription–export complex

mRNA recognition and packaging by the human transcription–export complex

Mechanomemory in protein diffusivity of chromatin and nucleoplasm after force cessation

How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell

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