Evidence map›Paper›PMID 19591840›Full record

ArticleJournal of molecular biology2009

Minimum-energy path for a u6 RNA conformational change involving protonation, base-pair rearrangement and base flipping.

Vincenzo Venditti, Lawrence Clos, Neri Niccolai, Samuel E Butcher

Abstract read
In one paragraph

Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Structure and conformational plasticity of the U6 small nuclear ribonucleoprotein core.Acta crystallographica. Section D, Structural biology · 2017
    Article
  9. Review
  10. Article
  11. Article
  12. Hierarchy of RNA functional dynamics.Annual review of biochemistry · 2014
    Review
  13. NMR studies of nucleic acid dynamics.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2013
    Article
  14. Article
  15. Article
  16. Structural analyses of the pre-mRNA splicing machinery.Protein science : a publication of the Protein Society · 2013
    Review
  17. Article
  18. Review
  19. Article
  20. Review
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

4 authors.

Vincenzo VendittiBiomolecular Structure Research Center and Dipartimento di Biologia Molecolare, Università di Siena, Italy.
Lawrence Clos
Neri Niccolai
Samuel E Butcher

Funding

WATER DISTRIB:PHYSICAL PROPERT:PIZZA &LMPS MOZZARELLA CHEESES:EARLY STAGE MATURP41RR002301 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 1985 to 2011
$13.0M
900 MHz NMR Spectrometer Biomolecular InvestigationsP41GM066326 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN L · 2002 to 2006
$5.0M
Structure and Function of U6 Spliceosomal RNAR01GM065166 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BROW, DAVID A, BUTCHER, SAMUEL E · 2002 to 2016
$3.5M
WIDE-BORE 9.4 TESLA NMR SPECTROMETER FOR UW-MADISONS10RR002781 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI MARKLEY, JOHN L · 1986 to 1986
–
CONSOLE UPGRADES FOR NMR FACILITYS10RR008438 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI MARKLEY, JOHN L · 1993 to 1993
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NCRR NIH HHS P41 RR002301NCRR NIH HHS P41RR02301NCRR NIH HHS RR0278NCRR NIH HHS S10 RR002781NCRR NIH HHS S10 RR008438NIGMS NIH HHS P41 GM066326NIGMS NIH HHS P41GM66326NIGMS NIH HHS R01 GM065166NIGMS NIH HHS R01 GM65166
6 · The paper itself

Abstract

The U6 RNA internal stem-loop (U6 ISL) is a highly conserved domain of the spliceosome that is important for pre-mRNA splicing. The U6 ISL contains an internal loop that is in equilibrium between two conformations controlled by the protonation state of an adenine (pK(a)=6.5). Lower pH favors formation of a protonated C-A(+) wobble pair and base flipping of the adjacent uracil. Higher pH favors stacking of the uracil and allows an essential metal ion to bind at this position. Here, we define the minimal-energy path for this conformational transition. To do this, we solved the U6 ISL structure at higher pH (8.0) in order to eliminate interference from the low-pH conformer. This structure reveals disruption of the protonated C-A(+) pair and formation of a new C-U pair, which explains the preference for a stacked uracil at higher pH. Next, we used nudged elastic band molecular dynamics simulations to calculate the minimum-energy path between the two conformations. Our results indicate that the C-U pair is dynamic, which allows formation of the more stable C-A(+) pair upon adenine protonation. After formation of the C-A(+) pair, the unpaired uracil follows a minor-groove base-flipping pathway. Molecular dynamics simulations suggest that the extrahelical uracil is stabilized by contacts with the adjacent helix.

Indexed as

Nucleic Acid ConformationBase PairingHydrogen-Ion ConcentrationModels, MolecularMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularProtonsRNA, Small NuclearSaccharomyces cerevisiaeThermodynamicsProtonsRNA, Small NuclearU6 small nuclear RNA

Identifiers

PMID19591840
PMCPMC2799254

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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.