The crystal structure of Staufen1 in complex with a physiological RNA sheds light on substrate selectivity

Lazzaretti, D.; Bandholz-Cajamarca, L.; Emmerich, Christiane; Schaaf, Kristina; Basquin, Claire; Irion, Uwe; Bono, Fulvia

doi:10.26508/lsa.201800187

Cited by 17 publications

(28 citation statements)

References 102 publications

(204 reference statements)

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“…Thus, a stem of 8 bp appears to be the minimal length required for recognition by mStau2 tandem domains. Of note, available structures of dsRBDs show binding to longer RNA stem loop of about 19 bp length 30,31 . It is therefore well possible that our observed binding to a minimal stem-loop RNA only reflects a partial recognition and that for a full binding a longer stem is required.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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Throughout metazoans, Staufen (Stau) proteins are core factors of mRNA localization particles. They consist of three to four double-stranded RNA binding domains (dsRBDs) and a C-terminal dsRBD-like domain. Mouse Staufen2 (mStau2)-like Drosophila Stau (dmStau) contains four dsRBDs. Existing data suggest that only dsRBDs 3–4 are necessary and sufficient for mRNA binding. Here, we show that dsRBDs 1 and 2 of mStau2 bind RNA with similar affinities and kinetics as dsRBDs 3 and 4. While RNA binding by these tandem domains is transient, all four dsRBDs recognize their target RNAs with high stability. Rescue experiments in Drosophila oocytes demonstrate that mStau2 partially rescues dmStau-dependent mRNA localization. In contrast, a rescue with mStau2 bearing RNA-binding mutations in dsRBD1–2 fails, confirming the physiological relevance of our findings. In summary, our data show that the dsRBDs 1–2 play essential roles in the mRNA recognition and function of Stau-family proteins of different species.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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“…Given the poor knowledge of the RNA structure within the cellular environment, proteins known to interact with RNAs adopting a stable secondary structure provide useful tools to identify targets folding as double‐stranded RNA within the cell. This is the case of Staufen‐1 (STAU1), a double‐stranded RBP (Figure b) mediating mRNA localization, stability, and translation in eukaryotic organisms . The study of RNAs crosslinked to STAU1 in living cells using hiCLIP (RNA hybrid and individual nucleotide resolution ultraviolet crosslinking and immunoprecipitation) followed by deep sequencing identified duplexes in ribosomal RNAs (rRNAs) and mRNAs .…”

Section: Relevance Of Rna Structure For Rbp Recognitionmentioning

confidence: 99%

“…This is the case of Staufen-1 (STAU1), a double-stranded RBP (Figure 1b) mediating mRNA localization, stability, and translation in eukaryotic organisms. [87,88] The study of RNAs crosslinked to STAU1 in living cells using hiCLIP (RNA hybrid and individual nucleotide resolution ultraviolet crosslinking and immunoprecipitation) followed by deep sequencing identified duplexes in ribosomal RNAs (rRNAs) and mRNAs. [89] Transcripts with duplexes on the 3′-UTR were enriched for protein trafficking, suggesting that they are translated on the ER, coincidentally with the subcellular localization of STAU1.…”

Section: Features Of the Rna Targets Of Roquin-1 And Staufen-1 Impactmentioning

confidence: 99%

Impact of RNA–Protein Interaction Modes on Translation Control: The Versatile Multidomain Protein Gemin5

2019

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The fate of cellular RNAs is largely dependent on their structural conformation, which determines the assembly of ribonucleoprotein (RNP) complexes. Consequently, RNA‐binding proteins (RBPs) play a pivotal role in the lifespan of RNAs. The advent of highly sensitive in cellulo approaches for studying RNPs reveals the presence of unprecedented RNA‐binding domains (RBDs). Likewise, the diversity of the RNA targets associated with a given RBP increases the code of RNA–protein interactions. Increasing evidence highlights the biological relevance of RNA conformation for recognition by specific RBPs and how this mutual interaction affects translation control. In particular, noncanonical RBDs present in proteins such as Gemin5, Roquin‐1, Staufen, and eIF3 eventually determine translation of selective targets. Collectively, recent studies on RBPs interacting with RNA in a structure‐dependent manner unveil new pathways for gene expression regulation, reinforcing the pivotal role of RNP complexes in genome decoding.

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“…Thus, a stem of 8 bp appears to be the minimal length required for recognition by mStau2 tandem domains. Of note, available structures of dsRBDs show binding to longer RNA stem-loops of about 19 bp length 48,49 . It is therefore well possible that our observed binding to a minimal stem-loop RNA only reflects a partial recognition and that for a full binding a longer stem is required.…”

Section: Role Of the Length Of Dsrna For Mstau2 Tandem Domain Bindingmentioning

confidence: 99%

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

Heber

Gáspár

Tants

et al. 2018

Preprint

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Throughout metazoans, Staufen (Stau) proteins are core factors of mRNA localization particles. They consist of three to four double-stranded RNA binding domains (dsRBDs) and a C-terminal dsRBD-like domain. Mouse Staufen2 (mStau2) like Drosophila Stau (dmStau) contains four dsRBDs. Existing data suggest that only dsRBDs 3-4 are necessary and sufficient for mRNA binding.Here, we show that dsRBDs 1 and 2 of mStau2 bind RNA with similar affinities and kinetics as dsRBDs 3 and 4. While RNA binding by these tandem domains is transient, all four dsRBDs recognize their target RNAs with high stability.Rescue experiments in Drosophila oocytes demonstrate that mStau2 partially rescues dmStau-dependent mRNA localization. In contrast, a rescue with mStau2 bearing RNA-binding mutations in dsRBD1-2 fails, confirming the physiological relevance of our findings. In summary, our data show that the dsRBDs 1-2 play essential roles in the mRNA recognition and function of Staufamily proteins of different species.

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The crystal structure of Staufen1 in complex with a physiological RNA sheds light on substrate selectivity

Abstract: Combination of in vitro and in vivo data show that RNA sequence influences Staufen target recognition and that protein–RNA base contacts are required for Staufen function in Drosophila.

Cited by 17 publications

References 102 publications

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

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

Impact of RNA–Protein Interaction Modes on Translation Control: The Versatile Multidomain Protein Gemin5

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

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