Evidence map›Paper›PMID 32929008›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Extracellular microRNAs in human circulation are associated with miRISC complexes that are accessible to anti-AGO2 antibody and can bind target mimic oligonucleotides.

Hirosha Geekiyanage, Shima Rayatpisheh, James A Wohlschlegel, Robert Brown, Victor Ambros

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% 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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.

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  16. Extracellular RNAs as Messengers and Early Biomarkers in Neurodegeneration.International journal of molecular sciences · 2025
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21 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Hirosha GeekiyanageDepartment of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.ORCID 0000-0002-7466-5983
Shima RayatpishehDepartment of Biological Chemistry, Geffen School of Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0003-3388-5776
James A WohlschlegelDepartment of Biological Chemistry, Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Robert BrownDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605.
Victor AmbrosDepartment of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605; victor.ambros@umassmed.edu.
University of Massachusetts Chan Medical School · USUniversity of California, Los Angeles · US

Funding

GENETIC CONTROL OF NEMATODE DEVELOPMENTR01GM034028 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI AMBROS, VICTOR · 1985 to 2018
$7.0M
Genetic control of developmental timingR35GM131741 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Victor Ambros · 2019 to 2026
$5.9M
Developmental Regulation of MicroRNA ExpressionR01GM088365 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI AMBROS, VICTOR · 2009 to 2010
$771k
NIGMS NIH HHS R01 GM034028NIGMS NIH HHS R01 GM088365NIGMS NIH HHS R35 GM131741
6 · The paper itself

Abstract

MicroRNAs (miRNAs) function cell-intrinsically to regulate gene expression by base-pairing to complementary mRNA targets while in association with Argonaute, the effector protein of the miRNA-mediated silencing complex (miRISC). A relatively dilute population of miRNAs can be found extracellularly in body fluids such as human blood plasma and cerebrospinal fluid (CSF). The remarkable stability of circulating miRNAs in such harsh extracellular environments can be attributed to their association with protective macromolecular complexes, including extracellular vesicles (EVs), proteins such as Argonaut 2 (AGO2), or high-density lipoproteins. The precise origins and the potential biological significance of various forms of miRNA-containing extracellular complexes are poorly understood. It is also not known whether extracellular miRNAs in their native state may retain the capacity for miRISC-mediated target RNA binding. To explore the potential functionality of circulating extracellular miRNAs, we comprehensively investigated the association between circulating miRNAs and the miRISC Argonaute AGO2. Using AGO2 immunoprecipitation (IP) followed by small-RNA sequencing, we find that miRNAs in circulation are primarily associated with antibody-accessible miRISC/AGO2 complexes. Moreover, we show that circulating miRNAs can base-pair with a target mimic in a seed-based manner, and that the target-bound AGO2 can be recovered from blood plasma in an ∼1:1 ratio with the respective miRNA. Our findings suggest that miRNAs in circulation are largely contained in functional miRISC/AGO2 complexes under normal physiological conditions. However, we find that, in human CSF, the assortment of certain extracellular miRNAs into free miRISC/AGO2 complexes can be affected by pathological conditions such as amyotrophic lateral sclerosis.

Indexed as

Amyotrophic Lateral SclerosisArgonaute ProteinsBase PairingCase-Control StudiesHumansImmunoprecipitationMicroRNAsAGO2 protein, humanArgonaute ProteinsMicroRNAsAGO2Argonautcerebrospinal fluidextracellular microRNAhuman plasma

Identifiers

PMID32929008
PMCPMC7533700
OpenAlexW3087580838

What Socratic 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 Socratic graph.