Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-β1

Cléry, Antoine; Jayne, Sandrine; Benderska, Natalya; Dominguez, Cyril; Stamm, Stefan; Allain, Frédéric H.‐T.

doi:10.1038/nsmb.2001

Cited by 101 publications

(139 citation statements)

References 58 publications

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“…In vitro Tra2␤ binding to E23 was dependent upon the sequence GCAAGAG within the E23 (19), a good match to the recently defined consensus sequences for mammalian Tra2␤ RNA binding defined by in vivo (24) and in vitro experiments (41,45). In toto, these results are consistent with Tra2␤ directly binding and activating Mypt1 E23 splicing in vivo, as we showed previously in vitro using splicing of a mini-gene transcript (19).…”

Section: Discussionsupporting

confidence: 77%

Tra2β Protein Is Required for Tissue-specific Splicing of a Smooth Muscle Myosin Phosphatase Targeting Subunit Alternative Exon

Mende

Bhetwal

et al. 2012

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 77%

Tra2β Protein Is Required for Tissue-specific Splicing of a Smooth Muscle Myosin Phosphatase Targeting Subunit Alternative Exon

Mende

Bhetwal

et al. 2012

Journal of Biological Chemistry

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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%

“…5a). The unusual orientation of the C-terminal loop and α-helix of Snu17p within the RNA-binding site suggests that the RES-RNA interaction is potentially another example of a noncanonical RRM-RNA recognition mode [38][39][40][49][50][51][52][53] . The increase in RNA affinity when c Pml1p is bound to c Snu17p and the C-terminal α-helix of Snu17p is formed (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

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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“…hTra2 functions as a splicing regulator, with its aberrant activity implicated in several diseases (Cle´ry et al, 2011;Gabriel et al, 2009;Hirschfeld et al, 2009;Hofmann et al, 2000;Sumner, 2007;Tsuda et al, 2011). The canonical hTra2 binding site is the (GAA) 2 repeat (Tsuda et al, 2011).…”

Section: Incorporating General External Informationmentioning

confidence: 99%

Site identification in high-throughput RNA–protein interaction data

et al. 2012

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Motivation: Post-transcriptional and co-transcriptional regulation is a crucial link between genotype and phenotype. The central players are the RNA-binding proteins, and experimental technologies [such as cross-linking with immunoprecipitation-(CLIP-) and RIP-seq] for probing their activities have advanced rapidly over the course of the past decade. Statistically robust, flexible computational methods for binding site identification from high-throughput immunoprecipitation assays are largely lacking however. Results: We introduce a method for site identification which provides four key advantages over previous methods: (i) it can be applied on all variations of CLIP and RIP-seq technologies, (ii) it accurately models the underlying read-count distributions, (iii) it allows external covariates, such as transcript abundance (which we demonstrate is highly correlated with read count) to inform the site identification process and (iv) it allows for direct comparison of site usage across cell types or conditions. Availability and implementation: We have implemented our method in a software tool called Piranha.

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Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-β1

Cited by 101 publications

References 58 publications

Tra2β Protein Is Required for Tissue-specific Splicing of a Smooth Muscle Myosin Phosphatase Targeting Subunit Alternative Exon

Tra2β Protein Is Required for Tissue-specific Splicing of a Smooth Muscle Myosin Phosphatase Targeting Subunit Alternative Exon

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

Site identification in high-throughput RNA–protein interaction data

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