Structural basis for RNA recognition by a type II poly(A)-binding protein

Song, Jikui; McGivern, Jered V.; Nichols, Karl W.; Markley, John L.; Sheets, Michael

doi:10.1073/pnas.0801274105

Cited by 21 publications

(33 citation statements)

References 34 publications

(42 reference statements)

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“…The fact that several oligomerization sites have been identified by independent approaches implicates a high propensity of PABPN1 to form oligomers and/or aggregates: (i) based on the crystal structure of the RNA binding domain, dimerization of the domain has been postulated (24). This assumption has been confirmed by the solution structure of the corresponding domain from Xenopus laevis (25). (ii) Two potential oligomerization sites have been detected via a yeast-two hybrid analysis to search for selfassociation of PABPN1 fragments.…”

supporting

confidence: 53%

Polyalanine-independent Conformational Conversion of Nuclear Poly(A)-binding Protein 1 (PABPN1)

Winter

Kühn

Hause

et al. 2012

Journal of Biological Chemistry

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Background: Mutations in the gene of the nuclear polyadenylate-binding protein 1 (PABPN1) lead to oculopharyngeal muscular dystrophy (OPMD) and aggregation of PABPN1. Results: Fibrillar structures occur independently of the OPMD causing mutation. Conclusion: OPMD might be caused by processes other than fibrillation. Significance: Fibrils of full-length PABPN1 have been obtained which might have structures identical to those found in OPMD patients.

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supporting

confidence: 53%

Polyalanine-independent Conformational Conversion of Nuclear Poly(A)-binding Protein 1 (PABPN1)

Winter

Kühn

Hause

et al. 2012

Journal of Biological Chemistry

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“…The PSPC1/NONO dimer, however, forms its highly constrained structure in the absence of nucleic acid. Furthermore, homodimeric RRM structures [e.g., EPABP2 (27) and RBM12 (PDB ID 2EK6)] dimerize directly via their RRMs. Conversely, and intriguingly, the two pseudosymmetrically related noncanonical RRM2 domains of PSPC1/ NONO form either side of a 20-Å solvent-filled channel at the center of the structure, and the two canonical RRM1 domains face outward (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation

Passon¹,

M²,

Rackham

et al. 2012

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

139

193

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Proteins of the Drosophila behavior/human splicing (DBHS) family include mammalian SFPQ (PSF), NONO (p54nrb), PSPC1, and invertebrate NONA and Hrp65. DBHS proteins are predominately nuclear, and are involved in transcriptional and posttranscriptional gene regulatory functions as well as DNA repair. DBHS proteins influence a wide gamut of biological processes, including the regulation of circadian rhythm, carcinogenesis, and progression of cancer. Additionally, mammalian DBHS proteins associate with the architectural long noncoding RNA NEAT1 (Menε/β) to form paraspeckles, subnuclear bodies that alter gene expression via the nuclear retention of RNA. Here we describe the crystal structure of the heterodimer of the multidomain conserved region of the DBHS proteins, PSPC1 and NONO. These proteins form an extensively intertwined dimer, consistent with the observation that the different DBHS proteins are typically copurified from mammalian cells, and suggesting that they act as obligate heterodimers. The PSPC1/NONO heterodimer has a right-handed antiparallel coiled-coil that positions two of four RNA recognition motif domains in an unprecedented arrangement on either side of a 20-Å channel. This configuration is supported by a protein:protein interaction involving the NONA/paraspeckle domain, which is characteristic of the DBHS family. By examining various mutants and truncations in cell culture, we find that DBHS proteins require an additional antiparallel coiled-coil emanating from either end of the dimer for paraspeckle subnuclear body formation. These results suggest that paraspeckles may potentially form through self-association of DBHS dimers into higher-order structures.gene regulation | nuclear organization | protein structure | RNA-binding proteins T he Drosophila behavior/human splicing (DBHS) proteins have been described as multifunctional nuclear proteins, implicated in subnuclear body formation; transcription initiation; coactivation and corepression; constitutive and alternative splicing; transcriptional termination; and DNA repair (1) and contributing to circadian rhythm regulation (2, 3), tumor suppression (4), and Drosophila behavior (5). Mammalian genomes encode three paralogous DBHS proteins: NONO, SFPQ, and PSPC1, whereas invertebrates encode one or two. NONO and SFPQ are highly abundant, expressed in a variety of cell lines and tissues (1). In contrast, PSPC1 is more selectively expressed, found at low levels in HeLa cells, but expressed at equal levels with NONO and SFPQ in sertoli cells of the testis, acting as a coactivator of transcription (6).Mammalian DBHS proteins are essential for the formation of subnuclear paraspeckles (7), where they interact with a longnoncoding RNA, NEAT1 (8-10), and influence its spatial arrangement (11). Paraspeckle formation is also dependent upon transcription of NEAT1, which acts as a structural scaffold, nucleating the bodies at least in part by recruiting DBHS proteins (12, 13). DBHS proteins functioning within paraspeckles bind to adenosine-to-inosine edited i...

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“…RRM domains of PABPs are known to specifically bind poly(A) RNA [12,13,34]. To tested whether the CsPABPN1 RRM domain would show similar properties, a truncated version of CsPABPN1 (CsPABPN1), carrying the entire RRM domain (Fig.…”

Section: The Rrm Domain Of Cspabpn1 Specifically Binds Poly(a) Wherementioning

confidence: 99%

Structure and Mechanism of Dimer–Monomer Transition of a Plant Poly(A)-Binding Protein upon RNA Interaction: Insights into Its Poly(A) Tail Assembly

Domingues

Sforça

Soprano

et al. 2015

Journal of Molecular Biology

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Poly(A)-binding proteins (PABPs) play crucial roles in mRNA biogenesis, stability, transport and translational control in most eukaryotic cells. Although animal PABPs are well-studied proteins, the biological role, three-dimensional structure and RNA-binding mode of plant PABPs remain largely uncharacterized. Here, we report the structural features and RNA-binding mode of a Citrus sinensis PABP (CsPABPN1). CsPABPN1 has a domain architecture of nuclear PABPs (PABPNs) with a single RNA recognition motif (RRM) flanked by an acidic N-terminus and a GRPF-rich C-terminus. The RRM domain of CsPABPN1 displays virtually the same three-dimensional structure and poly(A)-binding mode of animal PABPNs. However, while the CsPABPN1 RRM domain specifically binds poly(A), the full-length protein also binds poly(U). CsPABPN1 localizes to the nucleus of plant cells and undergoes a dimer-monomer transition upon poly(A) interaction. We show that poly(A) binding by CsPABPN1 begins with the recognition of the RNA-binding sites RNP1 and RNP2, followed by interactions with residues of the β2 strands, which stabilize the dimer, thus leading to dimer dissociation. Like human PABPN1, CsPABPN1 also seems to form filaments in the presence of poly(A). Based on these data, we propose a structural model in which contiguous CsPABPN1 RRM monomers wrap around the RNA molecule creating a superhelical structure that could not only shield the poly(A) tail but also serve as a scaffold for the assembly of additional mRNA processing factors.

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Structural basis for RNA recognition by a type II poly(A)-binding protein

Cited by 21 publications

References 34 publications

Polyalanine-independent Conformational Conversion of Nuclear Poly(A)-binding Protein 1 (PABPN1)

Polyalanine-independent Conformational Conversion of Nuclear Poly(A)-binding Protein 1 (PABPN1)

Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation

Structure and Mechanism of Dimer–Monomer Transition of a Plant Poly(A)-Binding Protein upon RNA Interaction: Insights into Its Poly(A) Tail Assembly

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