Functional stabilization of an RNA recognition motif by a noncanonical N-terminal expansion

Netter, C.; Weber, Gert; Benecke, Heike; Wahl, Markus C.

doi:10.1261/rna.1359909

Cited by 18 publications

(23 citation statements)

References 48 publications

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“…It is tempting to speculate that the canonical folding of RRM3 modulates the RNA binding capability of TIA-1 according to small pH changes (around the physiological value). Even though the extra RRM3 ␣-helix (␣ 1 ) fails in binding directly to RNA oligonucleotides, its relative orientation regarding ␣ 3 and ␤ 4 could facilitate stable RNA binding (30). A similar effect has been recently reported for the transcription factor EGR1 (early growth response protein 1) in its binding to DNA (31).…”

Section: Resultsmentioning

confidence: 52%

RNA Binding of T-cell Intracellular Antigen-1 (TIA-1) C-terminal RNA Recognition Motif Is Modified by pH Conditions

Cruz-Gallardo

Aroca

Persson

et al. 2013

Journal of Biological Chemistry

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Background: T-cell intracellular antigen-1 (TIA-1) is a key DNA/RNA-binding protein in RNA metabolism. Results: Binding of the TIA-1 RRM3 domain (isolated or fused to RRM2) to RNA is affected by pH changes. Conclusion:The pH dependence of the RRM3/RNA interaction may have a significant effect on the overall TIA-1 function. Significance: Unveiling the auxiliary role of RRM3 in RNA recognition sheds light on the TIA-1 function between cell compartments.

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Section: Resultsmentioning

confidence: 52%

RNA Binding of T-cell Intracellular Antigen-1 (TIA-1) C-terminal RNA Recognition Motif Is Modified by pH Conditions

Cruz-Gallardo

Aroca

Persson

et al. 2013

Journal of Biological Chemistry

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“…RNPC3 is a member of the minor spliceosome complex that participates in removal of U12-type introns from pre-mRNA (12,13). To confirm that these autoantibodies could be detected by standard methods, we performed immunoprecipitations on RNPC3 expressed by IVTT on the entire group of 48 samples.…”

Section: Resultsmentioning

confidence: 99%

Systematic autoantigen analysis identifies a distinct subtype of scleroderma with coincident cancer

Shah

et al. 2016

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

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Scleroderma is a chronic autoimmune rheumatic disease associated with widespread tissue fibrosis and vasculopathy. Approximately two-thirds of all patients with scleroderma present with three dominant autoantibody subsets. Here, we used a pair of complementary high-throughput methods for antibody epitope discovery to examine patients with scleroderma with or without known autoantibody specificities. We identified a specificity for the minor spliceosome complex containing RNA Binding Region (RNP1, RNA recognition motif) Containing 3 (RNPC3) that is found in patients with scleroderma without known specificities and is absent in unrelated autoimmune diseases. We found strong evidence for both intra- and intermolecular epitope spreading in patients with RNA polymerase III (POLR3) and the minor spliceosome specificities. Our results demonstrate the utility of these technologies in rapidly identifying antibodies that can serve as biomarkers of disease subsets in the evolving precision medicine era.

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“…Deletion of this region abolished binding of Pml1p to Snu17p 13,15 . RRM extensions, as observed in Snu17p, are already folded in an RRM's free state [34][35][36] or fold upon binding to RNA and protein 32,33,[37][38][39] . For example, two short C-terminal helices of U1A provide an additional RNA interface for the interaction of its RRM domain with RNA 36,40 .…”

Section: Discussionmentioning

confidence: 95%

Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex

Wysoczanski

Schneider

Munari

et al. 2014

Nat Struct Mol Biol

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1 1 a r t i c l e sSplicing entails the removal of introns from pre-mRNAs to generate exon-only mRNA, which is exported out of the nucleus for translation 1 . The splicing process is driven and controlled by a large and dynamic RNA-protein complex, the spliceosome 1,2 . The composition and structure of the spliceosome undergoes multiple rearrangements during a splicing reaction, in which a set of distinct structural and compositional states, designated as E, A, B act , B* and C complexes, can be defined 1 . As part of this process, small nuclear ribonucleoprotein (snRNP) particles and non-snRNP splice factors are recruited and released 1,2 . Although the organization of snRNP components of the spliceosome has received considerable attention in recent years, very little is known about the assembly, structure and dynamics of non-snRNP multimeric complexes.The non-snRNP RES complex is present in humans and yeast 3,4 . Deletion of RES genes slows splicing and leads to pre-mRNA leakage into the cytoplasm 3-5 . Distinct introns exhibit RES-dependent splicing 5-9 , as do pre-mRNAs encoding proteins functioning in RNA-nucleotide metabolism 8,10 . Components of the RES complex are found in B and C complexes of the spliceosome, in which RES can interact with U2 snRNP 4,11,12 . In yeast, the RES complex is composed of three proteins, snRNP-associated protein 17 (Snu17p, also known as Ist3p), pre-mRNA-leakage protein 1 (Pml1p) and bud siteselection protein 13 (Bud13p) 3,4 . Snu17p and Bud13p have been implicated directly in splicing 3,5,13 , whereas Pml1p has been linked to the retention of unspliced pre-mRNA in the nucleus 3,5 . Caenorhabditis elegans Bud13p is involved in embryogenesis 14 .Sequence analysis has indicated that Snu17p is a 148-residue (17.1-kDa) noncanonical member of the RRM family of proteins with a long C-terminal part, which exhibits low sequence similarity to published RRM structures 4 . Snu17p binds with nanomolar affinity to the 266-residue (30.5-kDa), natively disordered protein Bud13p 15 . The interaction has been postulated to involve a C-terminal UHM-ligand motif (ULM) in Bud13p that interacts with a U2AF-homology motif (UHM) in the RRM domain of Snu17p 13,15,16 . The only other identified domain encompasses a stretch of lysine residues at the N terminus of Bud13p. Binding of the third component, the 204-residue (23.4-kDa) Pml1p, occurs through its 50 N-terminal disordered residues. The remainder of Pml1p folds as a forkhead-associated domain 13,15,17 , which could potentially bind phosphopeptides 17 . Biochemical evidence has suggested that Snu17p acts as the central binding platform, which interacts with disordered parts of Bud13p and Pml1p 13,15,16 . The precise molecular architecture of the RES complex, however, has been elusive, and its RNA binding capabilities have remained unexplored.Here we solved the three-dimensional structure of the core of the RES complex and demonstrated that its assembly is driven by cooperativity that increases the binding affinity of the components of the complex ...

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Functional stabilization of an RNA recognition motif by a noncanonical N-terminal expansion

Cited by 18 publications

References 48 publications

RNA Binding of T-cell Intracellular Antigen-1 (TIA-1) C-terminal RNA Recognition Motif Is Modified by pH Conditions

RNA Binding of T-cell Intracellular Antigen-1 (TIA-1) C-terminal RNA Recognition Motif Is Modified by pH Conditions

Systematic autoantigen analysis identifies a distinct subtype of scleroderma with coincident cancer

Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex

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