It’s Not the Destination, It’s the Journey: Heterogeneity in mRNA Export Mechanisms

Scott, D.; Aguilar, Lisbeth-Carolina; Kramar, Mathew; Oeffinger, Marlene

doi:10.1007/978-3-030-31434-7_2

Cited by 15 publications

(16 citation statements)

References 214 publications

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“…Most mRNAs are exported from the nucleus to the cytoplasm as messenger ribonucleoprotein complexes (mRNPs) in a manner reliant on ATP-dependent events rather than Ran GTPase and karyopherins 37 . Following pre-messenger RNA processing, which typically includes 5’-capping, splicing, 3’-cleavage and polyadenylation, mature mRNPs associated with components of the TRanscription and Export (TREX), and Nuclear RNA export factor 1 / Nuclear Transport Factor 2 Like Export Factor 1 (NXF1/NXT1) complexes are irreversibly translocated to the cytoplasm 37 . In addition to the non-discriminatory bulk mRNA export pathway, metazoans have evolved selective mRNA export pathways, less well characterised.…”

Section: Figmentioning

confidence: 99%

“…These employ recruitment of RNA binding proteins via post-transcriptional modifications, structural and/or cis elements within the mRNA (named untranslated sequence elements for regulation, USER, codes; though some are embedded in coding sequence). USER codes promote coordinated export of functionally related mRNAs yet a single transcript can have multiple USER codes, which can synergise or compete, so some mRNAs may utilise several possible export pathways in accordance with export factor availability 37–39 . Some selective mRNA export mechanisms depend on specific nucleoporins or Exportin-1 (Xpo1/Crm1) 37, 38 .…”

Section: Figmentioning

confidence: 99%

“…mRNA export from the nucleus is coupled to pre-mRNA processing, including a checkpoint for completed splicing 31, 35, 37, 55 . Furthermore, and in line with proteomic downregulation of (m)RNA processing and metabolism components, we considered the possibility that the effect of altered nucleocytoplasmic transport on nuclear accumulation of poly(A) RNA in qNSCs might be due to limitation of mRNA export pathway components, upregulation of nuclear retention factors and/or incomplete splicing 37, 39 .…”

Section: Figmentioning

confidence: 99%

“…A few nucleoporins such as Nup96, Gle1, Nup155 and Tpr play key roles in mRNA export 37, 39 ; the latter two were detected and both downregulated (Supplementary Table 3). We detected 38 mRNA export factors 37, 39 of which 37 were downregulated in qNSCs (Fig. 5e, Supplementary Table 3).…”

Section: Figmentioning

confidence: 99%

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Neural stem cells alter nucleocytoplasmic partitioning and accumulate nuclear polyadenylated transcripts during quiescence

Rossi

Coum

Madelenat

et al. 2021

Preprint

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Quiescence is a cellular state characterised by reversible cell-cycle arrest and diminished biosynthetic activity that protects against environmental insults, replicative exhaustion and proliferation-induced mutations1. Entry into and exit from this state controls development, maintenance and repair of tissues plus, in the adult central nervous system, generation of new neurons and thus cognition and mood2-4. Cancer stem cells too can undergo quiescence, which confers them resistance to current therapies5,6. Despite clinical relevance, quiescence is poorly understood and is defined functionally given lack of molecular markers. Decrease of the most resource-intensive cellular process of protein synthesis is a feature of quiescence, controlled across species and cell types by inhibition of the Target of Rapamycin pathway1,7. Here, we combine Drosophila genetics and a mammalian model to show that altered nucleocytoplasmic partitioning and nuclear accumulation of polyadenylated RNAs are novel evolutionarily conserved hallmarks of quiescence regulation. These mechanisms provide a previously unappreciated regulatory layer to reducing protein synthesis in quiescent cells, whilst priming them for reactivation in response to appropriate cues.

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Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

See 2 more Smart Citations

Neural stem cells alter nucleocytoplasmic partitioning and accumulate nuclear polyadenylated transcripts during quiescence

Rossi

Coum

Madelenat

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…During their synthesis, processing and export, pre-mRNAs and mature mRNAs are packaged with RNA-binding proteins to form dynamic ribonucleoprotein particles (mRNPs) ( Mitchell and Parker, 2014 ; Singh et al, 2015 ; Tutucci and Stutz, 2011 ). The mRNA export machinery is highly conserved from yeast to humans and mainly depends on the export factor Mex67-Mtr2 (TAP-NXF1 in mammals) ( Niño et al, 2013 ; Scott et al, 2019 ; Wende et al, 2019 ). Mex67, in complex with Mtr2, mediates transport through the nuclear pore complex (NPC) via interactions with several FG-enriched nucleoporins (Nups) ( Santos-Rosa et al, 1998 ; Strässer et al, 2000a ; Terry et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

The deubiquitylase Ubp15 couples transcription to mRNA export

Eyboulet

Jeronimo

Côté

et al. 2020

eLife

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Nuclear export of messenger RNAs (mRNAs) is intimately coupled to their synthesis. pre-mRNAs assemble into dynamic ribonucleoparticles as they are being transcribed, processed, and exported. The role of ubiquitylation in this process is increasingly recognized but, while a few E3 ligases have been shown to regulate nuclear export, evidence for deubiquitylases is currently lacking. Here we identified deubiquitylase Ubp15 as a regulator of nuclear export in Saccharomyces cerevisiae. Ubp15 interacts with both RNA polymerase II and the nuclear pore complex, and its deletion reverts the nuclear export defect of E3 ligase Rsp5 mutants. The deletion of UBP15 leads to hyper-ubiquitylation of the main nuclear export receptor Mex67 and affects its association with THO, a complex coupling transcription to mRNA processing and involved in the recruitment of mRNA export factors to nascent transcripts. Collectively, our data support a role for Ubp15 in coupling transcription to mRNA export.

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Choosing the right exit: How functional plasticity of the nuclear pore drives selective and efficient mRNA export

2021

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The nuclear pore complex (NPC) serves as a central gate for mRNAs to transit from the nucleus to the cytoplasm. The ability for mRNAs to get exported is linked to various upstream nuclear processes including co-transcriptional RNP assembly and processing, and only export competent mRNPs are thought to get access to the NPC. While the nuclear pore is generally viewed as a monolithic structure that serves as a mediator of transport driven by transport receptors, more recent evidence suggests that the NPC might be more heterogenous than previously believed, both in its composition or in the selective treatment of cargo that seek access to the pore, providing functional plasticity to mRNA export. In this review, we consider the interconnected processes of nuclear mRNA metabolism that contribute and mediate export competence. Furthermore, we examine different aspects of NPC heterogeneity, including the role of the nuclear basket and its associated complexes in regulating selective and/or efficient binding to and transport through the pore.

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It’s Not the Destination, It’s the Journey: Heterogeneity in mRNA Export Mechanisms

Cited by 15 publications

References 214 publications

Neural stem cells alter nucleocytoplasmic partitioning and accumulate nuclear polyadenylated transcripts during quiescence

Neural stem cells alter nucleocytoplasmic partitioning and accumulate nuclear polyadenylated transcripts during quiescence

The deubiquitylase Ubp15 couples transcription to mRNA export

Choosing the right exit: How functional plasticity of the nuclear pore drives selective and efficient mRNA export

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