A structural model for the HAT domain of Utp6 incorporating bioinformatics and genetics

Champion, Erica A.; Kundrat, Lenka; Regan, Lynne; Baserga, Susan J.

doi:10.1093/protein/gzp022

Cited by 12 publications

(14 citation statements)

References 33 publications

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“…Utp18 bears a single WD domain preceded by ∼250 residues at the N-terminus. Utp6 is predicted to contain three HAT (half-a-tetratricopeptide) repeats at the middle region ( 15 , 16 ). The HAT repeats fold into elongated helical structures ( 17 , 18 ) and likely mediate protein interactions.…”

Section: Introductionmentioning

confidence: 99%

Integrative structural analysis of the UTPB complex, an early assembly factor for eukaryotic small ribosomal subunits

et al. 2016

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Ribosome assembly is an essential and conserved cellular process in eukaryotes that requires numerous assembly factors. The six-subunit UTPB complex is an essential component of the 90S precursor of the small ribosomal subunit. Here, we analyzed the molecular architecture of UTPB using an integrative structural biology approach. We mapped the major interactions that associate each of six UTPB proteins. Crystallographic studies showed that Utp1, Utp21, Utp12 and Utp13 are evolutionarily related and form a dimer of dimers (Utp1–Utp21, Utp12–Utp13) through their homologous helical C-terminal domains. Molecular docking with crosslinking restraints showed that the WD domains of Utp12 and Utp13 are associated, as are the WD domains of Utp1, Utp21 and Utp18. Electron microscopy images of the entire UTPB complex revealed that it predominantly adopts elongated conformations and possesses internal flexibility. We also determined crystal structures of the WD domain of Utp18 and the HAT and deviant HAT domains of Utp6. A structural model of UTPB was derived based on these data.

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Section: Introductionmentioning

confidence: 99%

Integrative structural analysis of the UTPB complex, an early assembly factor for eukaryotic small ribosomal subunits

et al. 2016

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“…Elucidating their biochemical functions during ribosome synthesis has been hampered by their large size, the transient nature of pre-ribosomes and the absence of evident enzymatic activities. Both complexes predominantly contain β-propeller and α-helical repeat structures, suggesting that they form a structural framework during early ribosome assembly 3 15 16 17 18 . Depletion experiments indicate that UtpA initiates pre-ribosome assembly by binding to the nascent pre-rRNA, and then recruits UtpB and the U3 snoRNP 9 19 .…”

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confidence: 99%

UtpA and UtpB chaperone nascent pre-ribosomal RNA and U3 snoRNA to initiate eukaryotic ribosome assembly

et al. 2016

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Early eukaryotic ribosome biogenesis involves large multi-protein complexes, which co-transcriptionally associate with pre-ribosomal RNA to form the small subunit processome. The precise mechanisms by which two of the largest multi-protein complexes—UtpA and UtpB—interact with nascent pre-ribosomal RNA are poorly understood. Here, we combined biochemical and structural biology approaches with ensembles of RNA–protein cross-linking data to elucidate the essential functions of both complexes. We show that UtpA contains a large composite RNA-binding site and captures the 5′ end of pre-ribosomal RNA. UtpB forms an extended structure that binds early pre-ribosomal intermediates in close proximity to architectural sites such as an RNA duplex formed by the 5′ ETS and U3 snoRNA as well as the 3′ boundary of the 18S rRNA. Both complexes therefore act as vital RNA chaperones to initiate eukaryotic ribosome assembly.

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“…Crystal structures of CstF-77 confirmed that HAT repeat tracts adopt a TPR-like structure (3, 4). The possibility that HAT repeat tracts might bind RNA has been suggested (1, 5-7), but the notion that HAT repeat tracts serve as a scaffold for binding other proteins dominates recent literature (3,(8)(9)(10)). This view is reflected by the annotation of the HAT motif at InterPro, which states only that "the repeats may be involved in protein-protein interactions" (http://www.ebi.…”

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confidence: 99%

RNA binding and RNA remodeling activities of the half-a-tetratricopeptide (HAT) protein HCF107 underlie its effects on gene expression

Hammani

Cook

Barkan

2012

Proc. Natl. Acad. Sci. U.S.A.

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The half-a-tetratricopeptide repeat (HAT) motif is a helical repeat motif found in proteins that influence various aspects of RNA metabolism, including rRNA biogenesis, RNA splicing, and polyadenylation. This functional association with RNA suggested that HAT repeat tracts might bind RNA. However, RNA binding activity has not been reported for any HAT repeat tract, and recent literature has emphasized a protein binding role. In this study, we show that a chloroplast-localized HAT protein, HCF107, is a sequence-specific RNA binding protein. HCF107 consists of 11 tandem HAT repeats and short flanking regions that are also predicted to form helical hairpins. The minimal HCF107 binding site spans ∼11 nt, consistent with the possibility that HAT repeats bind RNA through a modular one repeat-1 nt mechanism. Binding of HCF107 to its native RNA ligand in the psbH 5′ UTR remodels local RNA structure and protects the adjacent RNA from exonucleases in vitro. These activities can account for the RNA stabilizing, RNA processing, and translational activation functions attributed to HCF107 based on genetic data. We suggest that analogous activities contribute to the functions of HAT domains found in ribonucleoprotein complexes in the nuclear-cytosolic compartment.helical repeat protein | plastid | pentatricopeptide repeat T he half-a-tetratricopeptide (HAT) motif is a helical repeat motif that has been functionally linked to RNA because of its presence exclusively in complexes that influence RNA metabolism (1). Examples of HAT domain proteins include Utp6, which is involved in nuclear pre-rRNA processing, Prp6, which is involved in nuclear pre-mRNA splicing, and CstF-77, which is involved in pre-mRNA cleavage and polyadenylation. The HAT motif is related to the tetratricopeptide repeat (TPR), a degenerate 34-aa motif that forms a pair of antiparallel α-helices (reviewed in ref.2). TPR motifs are typically found in tandem arrays, which stack to form a broad surface that binds protein ligands. Crystal structures of CstF-77 confirmed that HAT repeat tracts adopt a TPR-like structure (3, 4). The possibility that HAT repeat tracts might bind RNA has been suggested (1, 5-7), but the notion that HAT repeat tracts serve as a scaffold for binding other proteins dominates recent literature (3,(8)(9)(10)). This view is reflected by the annotation of the HAT motif at InterPro, which states only that "the repeats may be involved in protein-protein interactions" (http://www.ebi. ac.uk/interpro/IEntry?ac=IPR003107).Although TPR, HEAT, and several other helical repeat motifs form protein binding surfaces, similar structures have been shown to bind nucleic acids. Puf and pentatricopeptide repeat (PPR) motifs have been shown to bind RNA (reviewed in refs. 11 and 12), and mTERF, ALK, and TAL repeat motifs have been shown to bind DNA (reviewed in refs. 13 and 14). Thus, it seemed quite plausible that the presence of HAT domains exclusively in ribonucleoprotein complexes reflects the fact that HAT repeat tracts interact directly with RNA. In this ...

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A structural model for the HAT domain of Utp6 incorporating bioinformatics and genetics

Cited by 12 publications

References 33 publications

Integrative structural analysis of the UTPB complex, an early assembly factor for eukaryotic small ribosomal subunits

Integrative structural analysis of the UTPB complex, an early assembly factor for eukaryotic small ribosomal subunits

UtpA and UtpB chaperone nascent pre-ribosomal RNA and U3 snoRNA to initiate eukaryotic ribosome assembly

RNA binding and RNA remodeling activities of the half-a-tetratricopeptide (HAT) protein HCF107 underlie its effects on gene expression

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