Evidence map›Paper›PMID 29662165›Full record

ArticleNature genetics2018

Deconvolution of seed and RNA-binding protein crosstalk in RNAi-based functional genomics.

Hiroshi I Suzuki, Ryan M Spengler, Giedre Grigelioniene, Tatsuya Kobayashi, Phillip A Sharp

Abstract read
In one paragraph

Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Review
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  14. MicroRNA Control of TGF-β Signaling.International journal of molecular sciences · 2018
    Review
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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.

Hiroshi I SuzukiDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4682-5086
Ryan M SpenglerDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Giedre GrigelionieneEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Tatsuya KobayashiEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Phillip A SharpDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. sharppa@mit.edu.ORCID http://orcid.org/0000-0003-1465-1691

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
REGULATION OF MRNA PROCESSINGR01GM034277 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHARP, PHILLIP A · 1985 to 2021
$8.0M
Stress and Proliferation States Impact MicroRNA-Mediated Regulation in CancerR01CA133404 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHARP, PHILLIP A · 2008 to 2017
$4.6M
Role of miR-17-92 miRNAs in skeletal development and bone homeostasisR01AR056645 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI KOBAYASHI, TATSUYA · 2010 to 2020
$4.1M
NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA133404NIAMS NIH HHS R01 AR056645NIGMS NIH HHS R01 GM034277
6 · The paper itself

Abstract

RNA interference (RNAi) is a major, powerful platform for gene perturbations, but is restricted by off-target mechanisms. Communication between RNAs, small RNAs, and RNA-binding proteins (RBPs) is a pervasive feature of cellular RNA networks. We present a crosstalk scenario, designated as crosstalk with endogenous RBPs' (ceRBP), in which small interfering RNAs or microRNAs with seed sequences that overlap RBP motifs have extended biological effects by perturbing endogenous RBP activity. Systematic analysis of small interfering RNA (siRNA) off-target data and genome-wide RNAi cancer lethality screens using 501 human cancer cell lines, a cancer dependency map, identified that seed-to-RBP crosstalk is widespread, contributes to off-target activity, and affects RNAi performance. Specifically, deconvolution of the interactions between gene knockdown and seed-mediated silencing effects in the cancer dependency map showed widespread contributions of seed-to-RBP crosstalk to growth-phenotype modulation. These findings suggest a novel aspect of microRNA biology and offer a basis for improvement of RNAi agents and RNAi-based functional genomics.

Indexed as

RNA InterferenceCell Line, TumorGenomicsHumansMicroRNAsNeoplasmsRNA-Binding ProteinsRNA, Small InterferingMicroRNAsRNA-Binding ProteinsRNA, Small Interfering

Identifiers

PMID29662165
PMCPMC5934319

What OpenQuestion holds

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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.