Affinage

SNRPA

U1 small nuclear ribonucleoprotein A · UniProt P09012

Length
282 aa
Mass
31.3 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNRPA (U1A) is a bifunctional RNA-binding protein that serves as a core U1 snRNP component required for pre-mRNA splicing and, in its snRNP-free form, acts as a regulator of polyadenylation and 3′-end processing. Its N-terminal RRM (RBD1) binds U1 snRNA hairpin II with ~20 pM affinity through a two-step 'lure-and-lock' mechanism: rapid electrostatic association is followed by conformational displacement of helix C from the β-sheet surface, enabling base stacking and hydrogen bonding with the conserved AUUGCAC loop motif (PMID:7984237, PMID:11297556, PMID:23703211). As a free protein, U1A cooperatively dimerizes via residues 103–119 on its own pre-mRNA PIE element and on other targets (IgM secretory poly(A) site, SMN 3′ UTR), directly contacting the C-terminal 20 residues of poly(A) polymerase to inhibit polyadenylation—a feedback circuit whose output depends on the ratio of non-snRNP U1A to available RNA-binding sites in each compartment (PMID:8458082, PMID:9087430, PMID:10742179, PMID:16373497). The snRNP-free SF-A complex containing U1A, PSF, and p54nrb additionally supports pre-mRNA cleavage during 3′-end formation, and U1A's interaction with SAM68 modulates U1 snRNP recruitment at specific 5′ splice sites, linking it to alternative splicing regulation (PMID:16373496, PMID:30767021).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1989 High

    Establishing what U1A recognizes on U1 snRNA and which protein motif is responsible resolved the fundamental question of how individual snRNP proteins are targeted to their cognate RNAs.

    Evidence In vitro RNA binding, site-directed mutagenesis, and deletion analysis of U1A and U1 snRNA hairpin II

    PMID:2531658

    Open questions at the time
    • No atomic-resolution view of the interface
    • Binding kinetics not yet measured
    • Role of C-terminal RRM unknown
  2. 1990 High

    Demonstrating that swapping just two nucleotides or eight amino acids reverses U1A/U2B″ RNA specificity established that a small number of residues encode the discrimination code between paralogous RNP proteins.

    Evidence Chimeric protein/RNA domain-swap experiments with in vitro binding assays

    PMID:2140872

    Open questions at the time
    • Structural basis for the specificity switch not resolved
    • In vivo consequences of specificity reversal not tested
  3. 1991 High

    Systematic mutagenesis and chemical protection mapped the individual residues and RNA backbone contacts essential for U1A–RNA recognition, preceding and guiding structural studies.

    Evidence Site-directed mutagenesis of RNP1/RNP2 residues combined with ethylation interference on hairpin II RNA

    PMID:1833186

    Open questions at the time
    • Conformational changes upon binding not yet detected
    • Role of helix C not identified
  4. 1992 High

    Quantitative thermodynamic analysis revealed an extraordinarily tight (~20 pM) interaction involving ~8 ion pairs, establishing U1A–hairpin II as one of the tightest known protein–RNA complexes and explaining its stability in the spliceosome.

    Evidence Nitrocellulose filter binding with salt-dependence analysis

    PMID:1508720

    Open questions at the time
    • Kinetic on/off rates not yet separated
    • Contribution of conformational change to affinity unknown
  5. 1992 High

    Demonstrating RNA-independent nuclear import via a large NLS element (residues 94–204) and compartment-dependent RNA-binding-site availability explained how U1A partitions between nuclear snRNP and cytoplasmic pools.

    Evidence Microinjection of deletion mutants with live cell imaging and RNA competition

    PMID:1618898

    Open questions at the time
    • Import receptor identity not yet determined
    • Mechanism coupling RNA availability to localization not molecularly defined
  6. 1993 High

    Discovery that U1A autoregulates its own mRNA by binding its 3′ UTR and inhibiting polyadenylation revealed a second, non-spliceosomal function and established a negative feedback loop for snRNP protein homeostasis.

    Evidence In vitro polyadenylation assays, RNA binding, and overexpression in mouse cells

    PMID:8262062 PMID:8458082

    Open questions at the time
    • Mechanism of PAP inhibition not resolved
    • Identity of other regulatory targets unknown
  7. 1994 High

    The crystal structure of U1A RBD1 bound to hairpin II RNA at 1.92 Å provided the first atomic view of an RRM–RNA complex, revealing base stacking with aromatic side chains on the β-sheet surface and extensive hydrogen bonding with the AUUGCAC loop.

    Evidence X-ray crystallography at 1.92 Å resolution

    PMID:7984237

    Open questions at the time
    • Free protein conformation not captured in this crystal form
    • Dynamics of helix C not visible
  8. 1994 High

    Identifying direct U1A–PAP protein interaction as the mechanism of polyadenylation inhibition—without blocking CPSF or cleavage—resolved how a small RNA-binding protein can specifically shut down poly(A) tail addition.

    Evidence In vitro polyadenylation with domain deletions, direct pull-down, chimeric yeast PAP

    PMID:8313473

    Open questions at the time
    • Structural basis of U1A–PAP contact not determined
    • In vivo stoichiometry not established
  9. 1995 Medium

    Showing that the C-terminal RRM (RBD2) does not bind any tested RNA despite a canonical RRM fold established it as a non-functional RNA-binding domain, focusing mechanistic attention on the N-terminal RRM and inter-domain linker for all known activities.

    Evidence NMR secondary structure determination with comprehensive in vitro RNA binding panel

    PMID:7723028

    Open questions at the time
    • Possible non-RNA ligands for RBD2 not excluded
    • Potential protein–protein interaction role not tested
  10. 1996 High

    NMR of free U1A revealed that helix C occludes the RNA-binding β-sheet and rotates ~135° upon RNA binding, establishing the conformational gating mechanism that controls access to the binding surface.

    Evidence Multidimensional heteronuclear NMR of U1A residues 2–117

    PMID:8609632

    Open questions at the time
    • Kinetic contribution of helix C displacement not yet measured
    • Link to PAP inhibition not yet made
  11. 1996 High

    Mapping the PAP-interacting surface to the C-terminal 20 residues of PAP and U1A residues 103–119, and showing that two U1A molecules must be bound for PAP interaction, defined the minimal molecular requirements for polyadenylation inhibition.

    Evidence GST pull-down of PAP C-terminal peptide, chimeric yeast/vertebrate PAP, mutagenesis, peptide inhibition

    PMID:9087430

    Open questions at the time
    • Atomic structure of U1A–PAP interface lacking
    • Whether the same U1A region mediates splicing coupling unclear
  12. 1997 High

    NMR of U1A–PIE RNA and identification of Leu-44 as the intrinsic specificity determinant for hairpin II vs. hairpin IV distinguished the structural basis for mRNA autoregulation from snRNP assembly recognition.

    Evidence NMR structure determination of U1A–PIE complex; chimeric protein binding assays with U2A′ addition

    PMID:9312034 PMID:9814759

    Open questions at the time
    • Full trimolecular complex structure not yet available
    • In vivo relevance of heterospecific U2 snRNA binding unclear
  13. 1998 Medium

    Identification of the SF-A complex (U1A + PSF) and its antibody-mediated inhibition of both splicing and polyadenylation revealed that snRNP-free U1A participates in a multi-protein complex linking 3′-end processing to splicing.

    Evidence Co-immunoprecipitation and co-purification of SF-A; antibody inhibition of coupled in vitro splicing/polyadenylation

    PMID:9848648

    Open questions at the time
    • Full subunit composition of SF-A not defined
    • Whether antibody inhibition is specific to U1A epitope not fully controlled
  14. 2000 High

    The NMR structure of the (U1A)₂–PIE RNA trimolecular complex showed that RNA binding–induced helix C displacement simultaneously enables dimerization and exposes the PAP-interaction surface, coupling autoregulatory RNA sensing to effector function.

    Evidence NMR structure determination of the 38 kDa trimolecular complex

    PMID:10742179

    Open questions at the time
    • No ternary complex with PAP resolved
    • Dynamics of cooperativity transition not captured
  15. 2001 High

    Kinetic dissection by SPR formally demonstrated the two-step 'lure-and-lock' binding mechanism: electrostatic encounter complex followed by hydrogen-bond/stacking-dependent locking, with single mutations selectively uncoupling the two steps.

    Evidence Surface plasmon resonance with systematic U1A mutants under varying ionic strength

    PMID:11297556

    Open questions at the time
    • Single-molecule resolution of the two steps not achieved
    • Whether the same mechanism operates for PIE RNA not tested
  16. 2001 High

    Identifying importin α/β and Ran as the nuclear import machinery for U1A, with NLS mapping to residues 100–144, resolved the transport pathway that controls the nuclear–cytoplasmic distribution of snRNP-free U1A.

    Evidence In vitro import reconstitution with recombinant importins, dominant-negative Ran in living cells, co-binding assays

    PMID:11278401

    Open questions at the time
    • Export pathway not identified
    • Regulation of import during differentiation not addressed
  17. 2004 High

    Demonstrating that U1A binds AUGC-containing motifs downstream of the IgM secretory poly(A) site and inhibits CstF-64 binding extended the autoregulatory paradigm to a physiologically regulated target, linking U1A levels to immunoglobulin class switching.

    Evidence In vitro RNA binding, cleavage assays, and competition binding

    PMID:15226420

    Open questions at the time
    • In vivo confirmation of U1A-dependent IgM poly(A) site regulation incomplete
    • Structural basis of CstF-64 displacement not resolved
  18. 2006 High

    Full characterization of the SF-A complex (U1A, PSF, p54nrb, p68) and demonstration that p54nrb is required for SF-A-dependent cleavage during polyadenylation defined the non-snRNP U1A complex as a cleavage co-factor.

    Evidence TAP-tag purification, mass spectrometry, immunodepletion/reconstitution of in vitro polyadenylation

    PMID:16373496

    Open questions at the time
    • Direct contacts between subunits not mapped
    • Whether SF-A acts on all or only a subset of poly(A) sites unknown
  19. 2006 Medium

    Showing that non-snRNP U1A levels decline during B-cell differentiation and proportionally lose PAP-inhibitory activity provided the first evidence that developmental regulation of free U1A abundance controls poly(A) site choice in vivo.

    Evidence Immunopurification of endogenous non-snRNP U1A from B-cell lines at different stages; in vitro PAP inhibition

    PMID:16373497

    Open questions at the time
    • Mechanism controlling non-snRNP U1A levels during differentiation not identified
    • Global poly(A) site changes not profiled
  20. 2013 High

    Refined SPR kinetics of helix C mutants established that helix C contributes to complex stability primarily through intraprotein hydrogen bonds that lock the conformational change, rather than through the quadruple base-stacking interaction.

    Evidence Surface plasmon resonance with helix C truncation and disruption mutants

    PMID:23703211

    Open questions at the time
    • Free energy decomposition of locking step not complete
    • Whether helix C dynamics differ on PIE vs. hairpin II RNA not tested
  21. 2013 High

    Extending the polyadenylation-inhibitory function to the SMN 3′ UTR—where U1A blocks cleavage by CPSF rather than PAP activity—demonstrated target-dependent mechanistic variation and disease relevance for spinal muscular atrophy.

    Evidence In vitro RNA binding, cleavage/polyadenylation assays, overexpression altering SMN protein levels

    PMID:24362020

    Open questions at the time
    • Whether U1A-mediated SMN regulation operates in motor neurons in vivo not shown
    • Binding site structure on SMN 3′ UTR not resolved
  22. 2019 High

    Identification of SAM68 as a direct partner that recruits U1A (and thereby U1 snRNP) to specific 5′ splice sites established a mechanism by which RNA-binding proteins outside the spliceosome modulate splice-site recognition through U1A.

    Evidence Reciprocal co-IP, pull-down, domain deletion mapping, splicing reporter assays for mTor intron 5

    PMID:30767021

    Open questions at the time
    • Genome-wide scope of SAM68-U1A regulated splicing events unknown
    • Structural basis of SAM68 YY domain–RRM1 interaction not resolved
  23. 2024 Medium

    Demonstrating that SNRPA promotes ERCC1 exon 8 inclusion and that its mRNA is stabilized by m6A reader IGF2BP1/ELAVL1 linked SNRPA expression levels to DNA repair capacity and cisplatin resistance.

    Evidence CRISPR KO, shRNA knockdown, overexpression, RNA-seq, isoform-specific siRNA, and mouse xenograft

    PMID:39555714

    Open questions at the time
    • Direct mechanism of ERCC1 exon 8 inclusion by SNRPA not defined
    • Whether this involves U1 snRNP or free U1A not distinguished
    • Single-lab finding awaits independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the U1A–PAP inhibitory complex has never been determined, and the genome-wide landscape of non-snRNP U1A-regulated poly(A) sites and alternative splicing events remains undefined.
  • No atomic structure of U1A–PAP complex
  • No transcriptome-wide map of free U1A binding sites
  • Function of the C-terminal RRM (RBD2) remains unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 10 GO:0098772 molecular function regulator activity 5
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 10 R-HSA-8953854 Metabolism of RNA 10 R-HSA-392499 Metabolism of proteins 2
Partners
CSTF2KPNA1KPNB1NONOPAPOLAPSFSAM68
Complex memberships
SF-A complex (U1A/PSF/p54nrb/p68)U1 snRNP

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Crystal structure of the U1A N-terminal RNA-binding domain (RBD1) complexed with a 21-nucleotide U1 snRNA hairpin II at 1.92 Å resolution revealed that the 10-nucleotide RNA loop binds to the surface of the β-sheet as an open structure, with the AUUGCAC sequence interacting extensively with conserved RNP1 and RNP2 motifs and the C-terminal extension, through base stacking with aromatic side chains and direct/water-mediated hydrogen bonds. X-ray crystallography Nature High 7984237
1989 The RNA-binding site of U1A on U1 snRNA is hairpin II (positions 48–91), specifically the evolutionarily conserved loop sequence; the protein region required for binding consists of an ~80 amino acid RNP motif plus flanking residues, and point mutations in the conserved RNP1/RNP2 sequences abolish RNA binding. In vitro RNA binding assays, site-directed mutagenesis, deletion analysis The EMBO journal High 2531658
1990 U1A recognizes U1 snRNA independently, whereas U2B'' requires the accessory protein U2A' for specific binding to U2 snRNA; exchange of two nucleotides between the two RNAs or eight amino acids between the two proteins reverses binding specificity, establishing the molecular basis for RNA target discrimination. In vitro RNA binding, chimeric protein/RNA swapping experiments Nature High 2140872
1993 U1A protein autoregulates production of its own mRNA by binding two sites in the conserved 47 nt region of its 3' UTR (resembling the U1 snRNA binding site) and specifically inhibiting polyadenylation of U1A pre-mRNA; overexpression of U1A in mouse cells downregulates endogenous U1A mRNA. In vitro polyadenylation assay, overexpression in mouse cells, RNA binding studies Cell High 8458082
1994 U1A protein inhibits polyadenylation by directly interacting with mammalian poly(A) polymerase (PAP) when bound to U1A pre-mRNA; it does not prevent CPSF binding or pre-mRNA cleavage, but specifically blocks PAP activity through a direct protein–protein interaction, and domains were identified in both proteins required for this inhibition. In vitro polyadenylation assay, domain deletion/mutagenesis, direct protein–protein interaction (in vitro pull-down), yeast PAP transfer experiment Cell High 8313473
1991 Mutagenesis of the U1A RNA-binding surface identified specific residues critical for U1 RNA binding: Thr11→Val and Asn15→Val in RNP2 abolished binding; Arg52→Gln in RNP1 abolished binding, suggesting a salt bridge with RNA phosphates; ethylation protection mapped the RNA backbone contacts to the 3' two-thirds of loop II and the 5' stem. Site-directed mutagenesis, ethylation protection, in vitro RNA binding assays The EMBO journal High 1833186
1993 Two molecules of U1A protein bind cooperatively to a conserved secondary structure in the 3' UTR of U1A pre-mRNA (PIE RNA); binding of only a single U1A molecule is insufficient for efficient inhibition of polyadenylation, establishing that the two-molecule complex is the functional unit. In vitro RNA binding (gel mobility shift), enzymatic structure probing, mutagenesis, in vitro polyadenylation assay The EMBO journal High 8262062
1996 The C-terminal 20 amino acids of vertebrate PAP are essential for inhibition by U1A-RNA complex; transfer of these 20 residues to yeast PAP confers U1A-mediated inhibition; a GST fusion of these 20 PAP residues interacts in vitro with the U1A-RNA complex only when two U1A molecules are bound; U1A residues 103–119 are required for PAP inhibition, and this region is also involved in coupling splicing to 3'-end formation. Mutagenesis, in vitro pull-down (GST fusion), chimeric yeast/vertebrate PAP, in vitro polyadenylation assay, peptide inhibition Genes & development High 9087430
1992 U1A is actively transported to the nucleus by a process independent of U1 snRNA interaction; nuclear localization requires a large sequence element between amino acids 94 and 204; U1A shuttles between nucleus and cytoplasm and its intracellular distribution is determined by the number of available RNA-binding sites in each compartment. Microinjection, deletion mutant analysis, in vivo RNA binding competition, live cell imaging The Journal of cell biology High 1618898
2000 NMR structure of the 38 kDa (U1A)2–PIE RNA trimolecular complex revealed that cooperative binding of two U1A molecules depends on helix C (C-terminal to RBD1); RNA binding induces a conformational change in helix C that simultaneously enables cooperativity and exposes the PAP-interacting domain, ensuring PAP is inhibited only when U1A is bound to its mRNA. NMR structure determination of 38 kDa complex Nature structural biology High 10742179
1996 Solution NMR structure of U1A residues 2–117 showed the C-terminal helix (helix C, Asp90–Lys98) lies across the β-sheet in the free protein, occluding the RNA-binding surface by contacting Leu44, Phe56, and Ile58; upon RNA binding, helix C rotates ~135° away, allowing Tyr13, Phe56, and Gln54 to stack with RNA bases. Multidimensional heteronuclear NMR structure determination Journal of molecular biology High 8609632
1997 NMR and structural analysis of U1A bound to PIE RNA (internal loop of its own 3' UTR) revealed that specificity determinants in the variable loop 3 of the RNP domain define the geometry of the intermolecular interface, and unique electrostatic interactions with the RNA phosphodiester backbone contribute to discriminatory recognition. NMR structure determination, mutational analysis The EMBO journal High 9312034
2001 Binding of U1A to U1 hairpin II proceeds via two mechanistically distinct steps: a rapid electrostatically driven association step (slowed by charge neutralization or increased salt) followed by a locking step based on close-range hydrogen bonding and stacking interactions (reflected in dramatically increased dissociation when these are disrupted); single amino acid substitutions can selectively uncouple the two steps. Real-time surface plasmon resonance (Biacore) with site-directed mutants and ionic strength variation The Journal of biological chemistry High 11297556
2000 Fourteen residues in U1A (amino acids 103–119) are required for homodimerization, cooperative RNA binding to PIE RNA, and inhibition of polyadenylation; U1A dimerizes even when RNA-binding is abrogated; a dimer-interface peptide is a potent inhibitor of polyadenylation. Yeast two-hybrid, coselection assay, gel mobility shift, in vitro polyadenylation, peptide inhibition Molecular and cellular biology High 10688667
2001 Nuclear import of U1A is mediated by importin α/β and Ran; the nuclear localization signal maps to residues 100–144 of mouse U1A; U1A binds the C-terminal portion of importin α; in living cells, nuclear accumulation of full-length U1A is Ran-dependent and inhibited by the importin β-binding domain of importin α. Cytoplasmic injection of deletion mutants, in vitro nuclear import assay with recombinant importins, co-binding assay, dominant-negative Ran in living cells The Journal of biological chemistry High 11278401
2006 The snRNP-free form of U1A (SF-A) forms a complex with PSF, p54nrb, and p68; p54nrb is critical for the role of the SF-A complex in pre-mRNA cleavage during polyadenylation, as shown by immunodepletion and reconstitution experiments. TAP-tagging/affinity purification, mass spectrometry, immunodepletion/reconstitution in vitro polyadenylation assay RNA (New York, N.Y.) High 16373496
1998 The snRNP-free form of U1A (SF-A) co-purifies and co-immunoprecipitates with PSF (the largest component, p105), and MAb 12E12 specific to SF-A inhibits both splicing and polyadenylation in a coupled in vitro reaction, indicating a functional role of the SF-A complex in both processes. Co-immunoprecipitation, co-purification, in vitro coupled splicing/polyadenylation assay with antibody inhibition RNA (New York, N.Y.) Medium 9848648
2004 U1A binds two AUGCN(1-3)C motifs within the 29-nucleotide sequence between the two GU-rich regions downstream of the IgM secretory poly(A) site, inhibiting cleavage stimulatory factor 64K (CstF-64) binding and cleavage at that poly(A) site. In vitro RNA binding, cleavage assay, competition binding experiments Molecular and cellular biology High 15226420
2006 Non-snRNP U1A levels decrease during B-cell differentiation; endogenous non-snRNP U1A immunopurified from less differentiated cells inhibits poly(A) polymerase proportional to U1A recovered, demonstrating that available (non-snRNP) U1A level controls polyadenylation at the IgM secretory poly(A) site. Immunoprecipitation with cell-line-specific antibodies, in vitro polyadenylation inhibition assay with purified endogenous U1A, cold competitor RNA experiments RNA (New York, N.Y.) Medium 16373497
2013 U1A binds directly and with high affinity and specificity to the SMN 3' UTR adjacent to the polyadenylation site, independent of U1 snRNP, and inhibits polyadenylation by specifically blocking 3' cleavage by CPSF; excess U1A above U1 snRNA levels decreases SMN protein levels. In vitro RNA binding, in vitro polyadenylation/cleavage assay, overexpression experiments The Journal of biological chemistry High 24362020
2019 SAM68 directly interacts with U1A through its C-terminal tyrosine-rich (YY) domain binding to the RRM1 domain of U1A; this interaction promotes recruitment of U1 snRNP to the 5' splice site of mTor intron 5; deletion of the SAM68-U1A interaction domain or mutation of SAM68-binding sites in mTor intron 5 abrogates U1A recruitment and 5' splice site recognition, leading to premature termination and polyadenylation. Co-immunoprecipitation, pulldown, deletion/mutation analysis, splicing reporter assays Nucleic acids research High 30767021
2020 SNRPA binds directly to the G-quadruplex structure in the 5' UTR of BAG-1 mRNA, as shown by label-free RNA pulldown from colorectal cancer cell extracts followed by LC-MS/MS; knockdown of SNRPA modulates BAG-1 protein expression levels. RNA pulldown from cell extracts, LC-MS/MS, G-quadruplex mutant control RNA, knockdown experiments Biochimie Medium 32629040
2024 SNRPA promotes inclusion of ERCC1 exon 8, and its depletion causes ERCC1 exon 8 skipping and reduced ERCC1-XPF complex formation; SNRPA mRNA is stabilized by the m6A reader IGF2BP1 and RNA stabilizer ELAVL1, which promote cisplatin resistance in an SNRPA-dependent manner. CRISPR/Cas9 KO, shRNA knockdown, overexpression, RNA-seq, siRNA isoform-specific depletion, mouse xenograft model Advanced science Medium 39555714
1995 In vitro genetic selection identified four U1A residues important for specific binding to U1 hairpin II; Leu-49 disproportionately affects the rate of complex release (locking step), and a higher-affinity variant than wild-type emerged, showing U1A affinity has not been evolutionarily maximized. Phage display combinatorial library selection (in vitro genetic selection), RNA binding assays PNAS Medium 8524863
2007 A conserved U1 site (5'-splice-site-like sequence) in the 3' UTR of the human U1A gene acts synergistically with the nearby PIE element to inhibit nuclear polyadenylation (poly(A) tail addition), representing the first endogenous U1 site in a cellular gene. Reporter assays, mutagenesis, in vitro polyadenylation assay RNA (New York, N.Y.) Medium 17942741
1998 NMR structure of the U1A RBD1–PIE RNA complex was determined; hydrogen bonding and hydrophobic interactions at the interface were characterized, establishing the structural basis for recognition of the internal-loop RNA target by the same protein surface used for hairpin II binding. NMR structure determination Journal of biomolecular NMR High 9566313
2013 The C-terminal helix (helix C) of U1A RBD1 occludes the RNA-binding surface in the free protein; truncation or disruption of helix C increases the association rate (exposes the binding surface) but greatly reduces complex stability (loss of locking); disruption of the quadruple stacking interaction has minor kinetic effects compared with removal of intraprotein hydrogen bonds mediated by helix C. Surface plasmon resonance (Biacore) kinetics with helix C truncation/disruption mutants Nucleic acids research High 23703211
1997 A single leucine residue in U1A (Leu-44) is critical for intrinsic specificity for U1 hairpin II loop sequence over U2 hairpin IV; U2A' enables U2B'' to discriminate loop sequences but plays no role in stem discrimination; U2A' can also promote heterospecific U1A binding to U2 snRNA but requires ~500-fold higher concentration due to preference for U2B''. In vitro RNA binding assays with chimeric proteins, addition of purified U2A' RNA (New York, N.Y.) Medium 9814759
1992 The N-terminal RRM (102 amino acids) of U1A binds the U1 snRNA stem/loop II with a dissociation constant of ~20 pM in physiological conditions; the complex has a half-life of 5 minutes; at least 8 ion-pairs form upon complex formation; a single mutation in the RNA loop reduces affinity ~10-fold. Nitrocellulose filter binding, thermodynamic and salt-dependence analysis Nucleic acids research High 1508720
1995 The C-terminal RBD (RBD2) of human U1A does not bind U1, U2, or U5 snRNA, RNA hairpins, homopolymers, or random sequence RNAs despite adopting the canonical βαββαβ RRM fold with conserved RNP1/RNP2 sequences, establishing that RBD2 is a non-functional RNA-binding domain. NMR secondary structure determination, in vitro RNA binding assays (filter binding) Journal of molecular biology Medium 7723028

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin. Nature 803 7984237
1989 Identification of the RNA binding segment of human U1 A protein and definition of its binding site on U1 snRNA. The EMBO journal 302 2531658
1990 Major determinants of the specificity of interaction between small nuclear ribonucleoproteins U1A and U2B'' and their cognate RNAs. Nature 261 2140872
1993 The human U1 snRNP-specific U1A protein inhibits polyadenylation of its own pre-mRNA. Cell 196 8458082
1994 The human U1A snRNP protein regulates polyadenylation via a direct interaction with poly(A) polymerase. Cell 192 8313473
1991 Identification of molecular contacts between the U1 A small nuclear ribonucleoprotein and U1 RNA. The EMBO journal 178 1833186
1996 Solution structure of the N-terminal RNP domain of U1A protein: the role of C-terminal residues in structure stability and RNA binding. Journal of molecular biology 161 8609632
1997 Structural basis of the RNA-binding specificity of human U1A protein. The EMBO journal 145 9312034
1980 Nucleotide sequences of nuclear U1A RNAs from chicken, rat and man. Nucleic acids research 139 6159587
2000 Crystallization and structure determination of a hepatitis delta virus ribozyme: use of the RNA-binding protein U1A as a crystallization module. Journal of molecular biology 133 10623545
1992 Intracellular distribution of the U1A protein depends on active transport and nuclear binding to U1 snRNA. The Journal of cell biology 123 1618898
1999 An inhibitor of nuclear export activates the p53 response and induces the localization of HDM2 and p53 to U1A-positive nuclear bodies associated with the PODs. Experimental cell research 122 10222137
2000 The NMR structure of the 38 kDa U1A protein - PIE RNA complex reveals the basis of cooperativity in regulation of polyadenylation by human U1A protein. Nature structural biology 121 10742179
1992 Interaction of N-terminal domain of U1A protein with an RNA stem/loop. Nucleic acids research 114 1508720
1997 Involvement of the carboxyl terminus of vertebrate poly(A) polymerase in U1A autoregulation and in the coupling of splicing and polyadenylation. Genes & development 113 9087430
1994 Interaction of RNA hairpins with the human U1A N-terminal RNA binding domain. Biochemistry 113 7520277
1993 A complex secondary structure in U1A pre-mRNA that binds two molecules of U1A protein is required for regulation of polyadenylation. The EMBO journal 111 8262062
1994 The Drosophila sex determination gene snf encodes a nuclear protein with sequence and functional similarity to the mammalian U1A snRNP protein. Genes & development 88 7926776
1981 The conformation of chicken, rat and human U1A RNAs in solution. Nucleic acids research 86 6164982
2005 Mechanism of Lys48-linked polyubiquitin chain recognition by the Mud1 UBA domain. The EMBO journal 82 16138082
1994 NMR studies of U1 snRNA recognition by the N-terminal RNP domain of the human U1A protein. The EMBO journal 71 8070414
2006 The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA. Nucleic acids research 68 16407334
1999 Changes in side-chain and backbone dynamics identify determinants of specificity in RNA recognition by human U1A protein. Journal of molecular biology 67 10588900
1996 Structure of the polyadenylation regulatory element of the human U1A pre-mRNA 3'-untranslated region and interaction with the U1A protein. Biochemistry 67 8652566
2001 Two functionally distinct steps mediate high affinity binding of U1A protein to U1 hairpin II RNA. The Journal of biological chemistry 65 11297556
1984 Regulation of the trimethylamine N-oxide (TMAO) reductase in Escherichia coli: analysis of tor::Mud1 operon fusion. Molecular & general genetics : MGG 61 6387391
2000 Investigating the binding specificity of U1A-RNA by computational mutagenesis. Journal of molecular biology 60 10623503
2018 Spliceosomal protein U1A is involved in alternative splicing and salt stress tolerance in Arabidopsis thaliana. Nucleic acids research 59 29228330
1995 Solution structure of the ribosome-binding domain of E. coli translation initiation factor IF3. Homology with the U1A protein of the eukaryotic spliceosome. Journal of molecular biology 59 7490747
1995 Analysis of RNA-binding proteins by in vitro genetic selection: identification of an amino acid residue important for locking U1A onto its RNA target. Proceedings of the National Academy of Sciences of the United States of America 59 8524863
1999 RNA recognition by the human U1A protein is mediated by a network of local cooperative interactions that create the optimal binding surface. Journal of molecular biology 58 9878401
1995 An RBD that does not bind RNA: NMR secondary structure determination and biochemical properties of the C-terminal RNA binding domain from the human U1A protein. Journal of molecular biology 57 7723028
2005 13C NMR relaxation studies of RNA base and ribose nuclei reveal a complex pattern of motions in the RNA binding site for human U1A protein. Journal of molecular biology 54 15890361
2001 Molecular dynamics and thermodynamics of protein-RNA interactions: mutation of a conserved aromatic residue modifies stacking interactions and structural adaptation in the U1A-stem loop 2 RNA complex. Journal of the American Chemical Society 52 11456923
2018 SNRPA enhances tumour cell growth in gastric cancer through modulating NGF expression. Cell proliferation 49 30039889
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