Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains

Heber, Simone; Gáspár, Imre; Tants, Jan‐Niklas; Günther, Johannes; Moya, Sandra M. Fernandez; Janowski, Robert; Ephrussi, Anne; Sattler, Michael; Niessing, Dierk

doi:10.1038/s41467-019-09655-3

Cited by 20 publications

(25 citation statements)

References 51 publications

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“…During stage 9, not only the likelihood of Staufen association with oskar RNPs increased; the relative levels of Staufen per RNP were also higher than in the preceding stages (Fig 4B '). We previously observed the same behavior for overexpressed Staufen and mammalian Stau2 (Heber et al, 2019) . Notably, however, no or greatly reduced scaling of the Staufen signal with oskar mRNA content of the mRNPs was observed in the oocyte prior to the onset of oskar localization to the posterior (Fig 4B ').…”

Section: Staufen Dissociates Egl From Oskar Mrnps In the Oocytesupporting

confidence: 72%

“…Mammalian orthologues of Drosophila Staufen, mStau1 and mStau2, play roles in the bidirectional transport of CaMKIIα and Rgs4 mRNAs in dendrites (Bauer et al, 2019;Heraud-Farlow et al, 2013) and in Xenopus oocytes, Staufen is a component of Vg1 transport RNPs (Yoon and Mowry 2004) , indicating that Staufen's function as a regulator of RNP transport is evolutionarily conserved. Supporting this notion, mStau2 can partially substitute for Drosophila Staufen in oskar mRNA localization (Heber et al, 2019) . How Staufen proteins orchestrate mRNA trafficking processes is unclear.…”

Section: Introductionmentioning

confidence: 85%

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An RNA-based feed-forward mechanism ensures motor switching in oskar mRNA transport

Gáspár

Ephrussi

2021

Preprint

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The regulated recruitment and activity of motor proteins is crucial for intracellular transport of cargoes, including ribonucleoprotein complexes (RNP). Here we show that regulation of mRNP transport by the minus end-directed dynein motor complex in the Drosophila germline relies on the interplay of two double-stranded RNA binding proteins, Staufen and the dynein adaptor Egalitarian. Our quantitative in situ analysis shows that, in the nurse cells, Egalitarian associates with bicoid, oskar and staufen mRNAs, which consequently enrich in the oocyte. This results in ooplasmic accumulation of Staufen and its recruitment to the transcripts. We demonstrate that Staufen levels scale proportionately with RNA content in oskar mRNPs, and to a lesser extent in bicoid mRNPs. We show that enhanced recruitment of Staufen to oskar mRNPs results in dissociation of Egalitarian and a reduction in minus end-directed transport, although dynein remains associated with the RNPs. The downregulation of dynein activity prevents anterior accumulation of oskar mRNA, whose transport to the posterior is essential for localized production of Oskar protein. Our observations identify a feed-forward loop, whereby staufen mRNA localization and protein accumulation in the oocyte enable motor switching, promoting oskar mRNA localization to the posterior pole.

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Section: Staufen Dissociates Egl From Oskar Mrnps In the Oocytesupporting

confidence: 72%

Section: Introductionmentioning

confidence: 85%

An RNA-based feed-forward mechanism ensures motor switching in oskar mRNA transport

Gáspár

Ephrussi

2021

Preprint

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“…Staufen2 (STAU2) is doubtlessly present in many mRNA transport complexes. It directly binds localized mRNAs (Heber et al, 2019 ) and affects mRNA transport (Mallardo et al, 2003 ; Sharangdhar et al, 2017 ; Bauer et al, 2019 ; Chu et al, 2019 ) but to date no direct evidence exists for its interaction with motor proteins.…”

Section: Known and Potential Messenger Rna-motor Adaptorsmentioning

confidence: 99%

Mammalian Neuronal mRNA Transport Complexes: The Few Knowns and the Many Unknowns

Rodrigues

Grawenhoff

Baumann

et al. 2021

Front. Integr. Neurosci.

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Hundreds of messenger RNAs (mRNAs) are transported into neurites to provide templates for the assembly of local protein networks. These networks enable a neuron to configure different cellular domains for specialized functions. According to current evidence, mRNAs are mostly transported in rather small packages of one to three copies, rarely containing different transcripts. This opens up fascinating logistic problems: how are hundreds of different mRNA cargoes sorted into distinct packages and how are they coupled to and released from motor proteins to produce the observed mRNA distributions? Are all mRNAs transported by the same transport machinery, or are there different adaptors or motors for different transcripts or classes of mRNAs? A variety of often indirect evidence exists for the involvement of proteins in mRNA localization, but relatively little is known about the essential activities required for the actual transport process. Here, we summarize the different types of available evidence for interactions that connect mammalian mRNAs to motor proteins to highlight at which point further research is needed to uncover critical missing links. We further argue that a combination of discovery approaches reporting direct interactions, in vitro reconstitution, and fast perturbations in cells is an ideal future strategy to unravel essential interactions and specific functions of proteins in mRNA transport processes.

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“…The length of 90% of RNA duplexes bound by STAU1 range from 5 to 14 nt lacking a precise sequence specificity; however, duplexes can enclose extraordinarily long loop structures of several hundred nucleotides [ 140 ]. In Mammalia, two D. melanogaster Staufen paralogs, STAU1 and STAU2, are expressed that regulate the expression of partly overlapping sets of target mRNAs [ 182 ]. Like NMD, SMD depends on translation termination and requires the recruitment of UPF1 as well as its phosphorylation (probably) by SMG1 [ 183 ].…”

Section: Staufen-mediated Mrna Decay (Smd)mentioning

confidence: 99%

UPF1-Mediated RNA Decay—Danse Macabre in a Cloud

Lavysh

Neu‐Yilik

2020

Biomolecules

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Nonsense-mediated RNA decay (NMD) is the prototype example of a whole family of RNA decay pathways that unfold around a common central effector protein called UPF1. While NMD in yeast appears to be a linear pathway, NMD in higher eukaryotes is a multifaceted phenomenon with high variability with respect to substrate RNAs, degradation efficiency, effector proteins and decay-triggering RNA features. Despite increasing knowledge of the mechanistic details, it seems ever more difficult to define NMD and to clearly distinguish it from a growing list of other UPF1-mediated RNA decay pathways (UMDs). With a focus on mammalian NMD, we here critically examine the prevailing NMD models and the gaps and inconsistencies in these models. By exploring the minimal requirements for NMD and other UMDs, we try to elucidate whether they are separate and definable pathways, or rather variations of the same phenomenon. Finally, we suggest that the operating principle of the UPF1-mediated decay family could be considered similar to that of a computing cloud providing a flexible infrastructure with rapid elasticity and dynamic access according to specific user needs.

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Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains

Cited by 20 publications

References 51 publications

An RNA-based feed-forward mechanism ensures motor switching in oskar mRNA transport

An RNA-based feed-forward mechanism ensures motor switching in oskar mRNA transport

Mammalian Neuronal mRNA Transport Complexes: The Few Knowns and the Many Unknowns

UPF1-Mediated RNA Decay—Danse Macabre in a Cloud

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