Evidence map›Paper›PMID 34988468›Full record

ReviewCurrent research in structural biology2022

Mechanism of RNA recognition by a Musashi RNA-binding protein.

Jinan Wang, Lan Lan, Xiaoqing Wu, Liang Xu, Yinglong Miao

Open access · goldAbstract readReview
In one paragraph

Review in Current research in structural biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Predicting Biomolecular Binding Kinetics: A Review.Journal of chemical theory and computation · 2023
    Review
  7. Article
  8. Article
  9. Binding Analysis Using Accelerated Molecular Dynamics Simulations and Future Perspectives.Advances and applications in bioinformatics and chemistry : AABC · 2022
    Review
  10. Gaussian accelerated molecular dynamics (GaMD): principles and applications.Wiley interdisciplinary reviews. Computational molecular science
    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

5 authors at 1 institution in 1 country.

Jinan WangCenter for Computational Biology, University of Kansas, Lawrence, KS, 66047, USA.
Lan LanDepartment of Molecular Biosciences, University of Kansas, Lawrence, KS, 66047, USA.
Xiaoqing WuDepartment of Molecular Biosciences, University of Kansas, Lawrence, KS, 66047, USA.
Liang XuDepartment of Molecular Biosciences, University of Kansas, Lawrence, KS, 66047, USA.
Yinglong MiaoCenter for Computational Biology, University of Kansas, Lawrence, KS, 66047, USA.
University of Kansas · US

Funding

Molecular cancer therapy targeting HuR-ARE interactionR01CA191785 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI AUBE, JEFFREY, XU, LIANG · 2015 to 2019
$2.1M
Enhanced Sampling of G-Protein-Coupled Receptor-G Protein InteractionsR01GM132572 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MIAO, YINGLONG · 2019 to 2023
$1.5M
NCI NIH HHS R01 CA191785NIGMS NIH HHS R01 GM132572
6 · The paper itself

Abstract

The Musashi RNA-binding proteins (RBPs) regulate translation of target mRNAs and maintenance of cell stemness and tumorigenesis. Musashi-1 (MSI1), long considered as an intestinal and neural stem cell marker, has been more recently found to be over expressed in many cancers. It has served as an important drug target for treating acute myeloid leukemia and solid tumors such as ovarian, colorectal and bladder cancer. One of the reported binding targets of MSI1 is Numb, a negative regulator of the Notch signaling. However, the dynamic mechanism of Numb RNA binding to MSI1 remains unknown, largely hindering effective drug design targeting this critical interaction. Here, we have performed extensive all-atom microsecond-timescale simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method, which successfully captured multiple times of spontaneous and highly accurate binding of the Numb RNA from bulk solvent to the MSI1 protein target site. GaMD simulations revealed that Numb RNA binding to MSI1 involved largely induced fit in both the RNA and protein. The simulations also identified important low-energy intermediate conformational states during RNA binding, in which Numb interacted mainly with the β2-β3 loop and C terminus of MSI1. The mechanistic understanding of RNA binding obtained from our GaMD simulations is expected to facilitate rational structure-based drug design targeting MSI1 and other RBPs.

Indexed as

Binding pathway and mechanismFree energy landscapeGaussian accelerated molecular dynamicsMusashi RNA-binding proteinsProtein-RNA binding

Identifiers

PMID34988468
PMCPMC8695263
OpenAlexW4225646940

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.