Evidence map›Paper›PMID 33684393›Full record

ArticleJournal of molecular biology2021

HnRNP A1/A2 Proteins Assemble onto 7SK snRNA via Context Dependent Interactions.

Le Luo, Liang-Yuan Chiu, Andrew Sugarman, Paromita Gupta, Silvi Rouskin, Blanton S Tolbert

Open access · bronzeAbstract read
In one paragraph

Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Progress in 7SK ribonucleoprotein structural biology.Frontiers in molecular biosciences · 2023
    Review
  10. Article
  11. Article
  12. Review
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Le LuoDepartment of Chemistry, Case Western Reserve University, Cleveland, OH 44106, United States.
Liang-Yuan ChiuDepartment of Chemistry, Case Western Reserve University, Cleveland, OH 44106, United States.
Andrew SugarmanDepartment of Chemistry, Case Western Reserve University, Cleveland, OH 44106, United States.
Paromita GuptaWhitehead Institute for Biomedical Research, Cambridge, MA, United States.
Silvi RouskinWhitehead Institute for Biomedical Research, Cambridge, MA, United States.
Blanton S TolbertDepartment of Chemistry, Case Western Reserve University, Cleveland, OH 44106, United States. Electronic address: bst18@case.edu.
Case Western Reserve University · USWhitehead Institute for Biomedical Research · US

Funding

The Center for HIV RNA Studies (CRNA)P50GM103297 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAYIE, KWAKU · 2012 to 2016
$21.7M
Time resolved SAXS studies on the RP2/Arl3 complex pp.484-485P41GM103622 · NIGMS · ILLINOIS INSTITUTE OF TECHNOLOGY · PI IRVING, THOMAS C · 2012 to 2020
$11.9M
Structural Biophysics of HIV Splicing and Transcriptional ControlR01AI150830 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI TOLBERT, BLANTON SMITH · 2020 to 2023
$2.2M
Inhibitor of FtsZ Polymerization in M. tuberculosisR01AI050470 · NIAID · SOUTHERN RESEARCH INSTITUTE · PI REYNOLDS, ROBERT C · 2002 to 2004
$1.7M
NIAID NIH HHS R01 AI050470NIAID NIH HHS R01 AI150830NIGMS NIH HHS P41 GM103622NIGMS NIH HHS P50 GM103297
6 · The paper itself

Abstract

7SK small nuclear RNA (snRNA) is an abundant and ubiquitously expressed noncoding RNA that functions to modulate the activity of RNA Polymerase II (RNAPII) in part by stabilizing distinct pools of 7SK-protein complexes. Prevailing models suggest that the secondary structure of 7SK is dynamically remodeled within its alternative RNA-protein pools such that its architecture differentially regulates the exchange of cognate binding partners. The nuclear hnRNP A1/A2 proteins influence the biology of 7SK snRNA via processes that require an intact stem loop (SL) 3 domain; however, the molecular details by which hnRNPs assemble onto 7SK snRNA are yet to be described. Here, we have taken an integrated approach to present a detailed description of the 7SK-hnRNP A1 complex. We show that unbound 7SK snRNA adopts at least two major conformations in solution, with significant structural differences localizing to the SL2-3 linker and the base of SL3. Phylogenetic analysis indicates that this same region is the least genetically conserved feature of 7SK snRNA. By performing DMS modifications with the presence of excess protein, we reveal that hnRNP A1 binds with selectivity to SL3 through mechanisms that increase the flexibility of the RNA adjacent to putative binding sites. Calorimetric titrations further validate that hnRNP A1-SL3 assembly is complex with the affinity of discrete binding events modulated by the surrounding RNA structure. To interpret this context-dependent binding phenomenon, we determined a 3D model of SL3 to show that it folds to position minimal hnRNP A1/A2 binding sites (5'-Y/RAG-3') within different local environments. SL3-protein complexes resolved by SEC-MALS-SAXS confirm that up to four hnRNP A1 proteins bind along the entire surface of SL3 via interactions that preserve the overall structural integrity of this domain. In sum, the collective results presented here reveal a specific role for a folded SL3 domain to scaffold hnRNP A1/A2-7SK assembly via mechanisms modulated by the surrounding RNA structure.

Indexed as

Nucleic Acid ConformationAnimalsBase SequenceBinding SitesHeterogeneous Nuclear Ribonucleoprotein A1Heterogeneous-Nuclear Ribonucleoprotein Group A-BHumansMagnetic Resonance SpectroscopyModels, MolecularPositive Transcriptional Elongation Factor BProtein BindingRNA, Small NuclearSubstrate SpecificityHeterogeneous Nuclear Ribonucleoprotein A1Heterogeneous-Nuclear Ribonucleoprotein Group A-BhnRNP A2Positive Transcriptional Elongation Factor BRNA, Small Nuclear7SK snRNADMS-MaPseqhnRNP A1/A2 proteinsNMR spectroscopySAXS

Identifiers

PMID33684393
PMCPMC8091503
OpenAlexW3133996696

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.