Mechanism and Regulation of Co-transcriptional mRNP Assembly and Nuclear mRNA Export

Wende, Wolfgang; Friedhoff, Peter; Sträßer, Katja

doi:10.1007/978-3-030-31434-7_1

Cited by 37 publications

(39 citation statements)

References 203 publications

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“…Hence, our results indicate a novel role of Mex67 in stabilization of telomerase RNA which to our knowledge is the first time that Mex67 is implicated in a function distinct from RNA export. Mex67 is known to bind at least to some of its cargoes co-transcriptionally ( Dieppois et al, 2006 ; Wende et al, 2019 ). It has been proposed that such early association with its RNA substrates may assist in proper 3’-end RNA maturation and protection ( Forrester et al, 1992 ; Hammell et al, 2002 ; Qu et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex

Vasianovich

Bajon

Wellinger

2020

eLife

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The templating RNA is the core of the telomerase reverse transcriptase. In Saccharomyces cerevisiae, the complex life cycle and maturation of telomerase includes a cytoplasmic stage. However, timing and reason for this cytoplasmic passage are poorly understood. Here, we use inducible RNA tagging experiments to show that immediately after transcription, newly synthesized telomerase RNAs undergo one round of nucleo-cytoplasmic shuttling. Their export depends entirely on Crm1/Xpo1, whereas re-import is mediated by Kap122 plus redundant, kinetically less efficient import pathways. Strikingly, Mex67 is essential to stabilize newly transcribed RNA before Xpo1-mediated nuclear export. The results further show that the Sm7 complex associates with and stabilizes the telomerase RNA in the cytoplasm and promotes its nuclear re-import. Remarkably, after this cytoplasmic passage, the nuclear stability of telomerase RNA no longer depends on Mex67. These results underscore the utility of inducible RNA tagging and challenge current models of telomerase maturation.

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Section: Discussionmentioning

confidence: 99%

Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex

Vasianovich

Bajon

Wellinger

2020

eLife

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“…As the nascent transcript is synthesized by RNA polymerase II from the corresponding DNA template, it undergoes several chemical modifications, including 5' capping, splicing and 3'-end polyadenylation. Simultaneously, the nascent transcript associates with a cohort of complementary proteins to form a mature messenger ribonucleoprotein particle (mRNP) (Wende et al, 2019;Xie & Ren, 2019;Müller-McNicoll & Neugebauer, 2013;Meinel & Strässer, 2015;Singh et al, 2015;Wegener & Müller-McNicoll, 2018). The mature mRNP is then shuttled through the nuclear pore to the cytoplasm via specific export factors (Moore & Proudfoot, 2009;Müller-McNicoll & Neugebauer, 2013;Rondón, Jimeno, & Aguilera, 2010;Wende et al, 2019;Xie & Ren, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Data from both yeast and human studies have converged on the notion that THO binds Sub2, which in turn recruits Yra1 to form the TREX complex (Heath et al, 2016;Strässer et al, 2002;Wende et al, 2019;Zenklusen et al, 2002). This series of events is remarkably conserved in the human orthologues, the DNA-RNA helicase UAP56 (DDX39B) and the RNA-binding factor Aly/Ref (ALYREF) (Heath et al, 2016;Luo et al, 2001;Strässer et al, 2002;Wende et al, 2019). In this study, we identify the molecular mechanisms utilized by yeast THO to activate the unwinding properties of the Sub2 ATPase, thereby intimating how THO-containing complexes can fulfil their functions in R loop prevention and mRNP formation.…”

Section: Introductionmentioning

confidence: 99%

Structural insights into the nucleic acid remodeling mechanisms of the yeast THO-Sub2 complex

Schuller

Prabu

et al. 2020

eLife

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The yeast THO complex is recruited to active genes and interacts with the RNA-dependent ATPase Sub2 to facilitate the formation of mature export-competent messenger ribonucleoprotein particles and to prevent the co-transcriptional formation of RNA:DNA-hybrid-containing structures. How THO-containing complexes function at the mechanistic level is unclear. Here, we elucidated a 3.4 Å resolution structure of Saccharomyces cerevisiae THO-Sub2 by cryo-electron microscopy. THO subunits Tho2 and Hpr1 intertwine to form a platform that is bound by Mft1, Thp2, and Tex1. The resulting complex homodimerizes in an asymmetric fashion, with a Sub2 molecule attached to each protomer. The homodimerization interfaces serve as a fulcrum for a seesaw-like movement concomitant with conformational changes of the Sub2 ATPase. The overall structural architecture and topology suggest the molecular mechanisms of nucleic acid remodeling during mRNA biogenesis.

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“…In addition to protein complexes associating transiently with the mRNA for its processing (see Section 1.1 and Figure 2), nuclear mRNA-binding proteins bind stably to the mRNA forming an mRNP. This mRNP assembly occurs already co-transcriptionally, i.e., on the nascent mRNA [32][33][34][35][36]. The correct formation of the mRNP is a prerequisite for nuclear mRNA stability and nuclear mRNA export.…”

Section: Mrnp Assembly and Dynamicsmentioning

confidence: 99%

Dynamic mRNP Remodeling in Response to Internal and External Stimuli

et al. 2020

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Signal transduction and the regulation of gene expression are fundamental processes in every cell. RNA-binding proteins (RBPs) play a key role in the post-transcriptional modulation of gene expression in response to both internal and external stimuli. However, how signaling pathways regulate the assembly of RBPs with mRNAs remains largely unknown. Here, we summarize observations showing that the formation and composition of messenger ribonucleoprotein particles (mRNPs) is dynamically remodeled in space and time by specific signaling cascades and the resulting post-translational modifications. The integration of signaling events with gene expression is key to the rapid adaptation of cells to environmental changes and stress. Only a combined approach analyzing the signal transduction pathways and the changes in post-transcriptional gene expression they cause will unravel the mechanisms coordinating these important cellular processes.

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Mechanism and Regulation of Co-transcriptional mRNP Assembly and Nuclear mRNA Export

Cited by 37 publications

References 203 publications

Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex

Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex

Structural insights into the nucleic acid remodeling mechanisms of the yeast THO-Sub2 complex

Dynamic mRNP Remodeling in Response to Internal and External Stimuli

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