Abstract:Asymmetric ASH1 mRNA transport during mitosis of budding yeast constitutes one of the best-studied examples of mRNA localization. Recently, 2 studies used in vitro motility assays to prove that motile ASH1 mRNA-transport complexes can be reconstituted entirely from recombinant factors. Both studies, however, differed in their conclusions on whether cargo RNA itself is required for particle assembly and thus activation of directional transport. Here we provide direct evidence that stable complexes do assemble i… Show more
“…They however, reached contradicting conclusions on the role of ASH1 mRNA itself, with one study concluding that the mRNA itself is essential for processivity under physiological conditions to stabilise the transport complex [ 45 ], whereas the other argued that the cargo mRNA is dispensable for in vitro processivity [ 44 ]. It therefore remains unclear if the RNA moiety is essential for transport in living cells [ 47 , 48 ]. Fig.…”
Messenger RNA (mRNA) localisation enables a high degree of spatiotemporal control on protein synthesis, which contributes to establishing the asymmetric protein distribution required to set up and maintain cellular polarity. As such, a tight control of mRNA localisation is essential for many biological processes during development and in adulthood, such as body axes determination in Drosophila melanogaster and synaptic plasticity in neurons. The mechanisms controlling how mRNAs are localised, including diffusion and entrapment, local degradation and directed active transport, are largely conserved across evolution and have been under investigation for decades in different biological models. In this review, we will discuss the standing of the field regarding directional mRNA transport in light of the recent discovery that RNA can hitchhike on cytoplasmic organelles, such as endolysosomes, and the impact of these transport modalities on our understanding of neuronal function during development, adulthood and in neurodegeneration.
“…They however, reached contradicting conclusions on the role of ASH1 mRNA itself, with one study concluding that the mRNA itself is essential for processivity under physiological conditions to stabilise the transport complex [ 45 ], whereas the other argued that the cargo mRNA is dispensable for in vitro processivity [ 44 ]. It therefore remains unclear if the RNA moiety is essential for transport in living cells [ 47 , 48 ]. Fig.…”
Messenger RNA (mRNA) localisation enables a high degree of spatiotemporal control on protein synthesis, which contributes to establishing the asymmetric protein distribution required to set up and maintain cellular polarity. As such, a tight control of mRNA localisation is essential for many biological processes during development and in adulthood, such as body axes determination in Drosophila melanogaster and synaptic plasticity in neurons. The mechanisms controlling how mRNAs are localised, including diffusion and entrapment, local degradation and directed active transport, are largely conserved across evolution and have been under investigation for decades in different biological models. In this review, we will discuss the standing of the field regarding directional mRNA transport in light of the recent discovery that RNA can hitchhike on cytoplasmic organelles, such as endolysosomes, and the impact of these transport modalities on our understanding of neuronal function during development, adulthood and in neurodegeneration.
“…Recent in vitroreconstitution and single-particle motility assays demonstrated that these three proteins together with the myosin chaperone She4p and myosin light chains are sufficient to support processive transport of ASH1 mRNA along actin filaments. [41][42][43] In addition to this core complex, the transport particle is loaded with the translational repressors Dhh1p, Khd1p, and Puf6p [44][45][46][47][48] that ensure translational silencing of the transcript during transport 49 (Figure 1(c)). To release translational repression, Khd1p and Puf6p become phosphorylated by the casein kinases Yck1p and Yck2p.…”
Section: Localization Elements In Eukaryotesmentioning
confidence: 99%
“…As She3p is constitutively bound to the type V myosin motor Myo4p, the resulting complex consists of ASH1 mRNA, She2p, She3p, and Myo4p (Figure (b)). Recent in vitro ‐reconstitution and single‐particle motility assays demonstrated that these three proteins together with the myosin chaperone She4p and myosin light chains are sufficient to support processive transport of ASH1 mRNA along actin filaments …”
Section: Actin‐dependent Transport Of Mrnasmentioning
Eukaryotic cells rely on the precise determination of when and where proteins are synthesized. Spatiotemporal expression is supported by localization of mRNAs to specific subcellular sites and their subsequent local translation. This holds true for somatic cells as well as for oocytes and embryos. Most commonly, mRNA localization is achieved by active transport of the molecules along the actin or microtubule cytoskeleton. Key factors are molecular motors, adaptors, and RNA-binding proteins that recognize defined sequences or structures in cargo mRNAs. A deep understanding of this process has been gained from research on fungal model systems such as Saccharomyces cerevisiae and Ustilago maydis. Recent highlights of these studies are the following: (1) synergistic binding of two RNA-binding proteins is needed for high affinity recognition; (2) RNA sequences undergo profound structural rearrangements upon recognition; (3) mRNA transport is tightly linked to membrane trafficking; (4) mRNAs and ribosomes are transported on the cytoplasmic surface of endosomes; and (5) heteromeric protein complexes are, most likely, assembled co-translationally during endosomal transport. Thus, the study of simple fungal model organisms provides valuable insights into fundamental mechanisms of mRNA transport boosting the understanding of similar events in higher eukaryotes.
mRNA localization is an essential mechanism of gene regulation and is required for processes such as stem-cell division, embryogenesis and neuronal plasticity. It is not known which features in the cis-acting mRNA localization elements (LEs) are specifically recognized by motor-containing transport complexes. To the best of our knowledge, no high-resolution structure is available for any LE in complex with its cognate protein complex. Using X-ray crystallography and complementary techniques, we carried out a detailed assessment of an LE of the ASH1 mRNA from yeast, its complex with its shuttling RNA-binding protein She2p, and its highly specific, cytoplasmic complex with She3p. Although the RNA alone formed a flexible stem loop, She2p binding induced marked conformational changes. However, only joining by the unstructured She3p resulted in specific RNA recognition. The notable RNA rearrangements and joint action of a globular and an unfolded RNA-binding protein offer unprecedented insights into the step-wise maturation of an mRNA-transport complex.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
