A functional riboSNitch in the 3'UTR of FKBP5 alters microRNA-320a binding efficiency and mediates vulnerability to chronic posttraumatic pain. (Record no. 3692)

MARC details
000 -LEADER
fixed length control field 04944nam a22006137a 4500
008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION
fixed length control field 180831s20182018 xxu||||| |||| 00| 0 eng d
022 ## - INTERNATIONAL STANDARD SERIAL NUMBER
International Standard Serial Number 0270-6474
024 ## - OTHER STANDARD IDENTIFIER
Standard number or code 10.1523/JNEUROSCI.3458-17.2018 [doi]
024 ## - OTHER STANDARD IDENTIFIER
Standard number or code JNEUROSCI.3458-17.2018 [pii]
040 ## - CATALOGING SOURCE
Original cataloging agency Ovid MEDLINE(R)
099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC)
PMID 30150364
245 ## - TITLE STATEMENT
Title A functional riboSNitch in the 3'UTR of FKBP5 alters microRNA-320a binding efficiency and mediates vulnerability to chronic posttraumatic pain.
251 ## - Source
Source Journal of Neuroscience. 38(39):8407-8420, 2018 09 26.
252 ## - Abbreviated Source
Abbreviated source J Neurosci. 38(39):8407-8420, 2018 09 26.
253 ## - Journal Name
Journal name The Journal of neuroscience : the official journal of the Society for Neuroscience
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Year 2018
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Manufacturer FY2019
265 ## - SOURCE FOR ACQUISITION/SUBSCRIPTION ADDRESS [OBSOLETE]
Publication status aheadofprint
266 ## - Date added to catalog
Date added to catalog 2018-08-31
501 ## - WITH NOTE
Local holdings Available online from MWHC library: 1981 - present (after 18 months)
520 ## - SUMMARY, ETC.
Abstract Copyright (c) 2018 the authors.
520 ## - SUMMARY, ETC.
Abstract Previous studies have shown that common variants of the gene coding for FK506 binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant due to its effect on gene methylation. We here report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and posttraumatic chronic pain in 1,607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico,in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe posttraumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistence. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress and pain-associated microRNA, miR-320a, to FKBP5 via altering FKBP5 mRNA 3'UTR secondary structure (i.e. is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene-miRNA interaction influencing chronic pain risk in vulnerable individuals and suggests that exogenous methods to achieve targeted reduction in post-stress FKBP5 mRNA expression may constitute useful therapeutic strategies.<b>Significance statement:</b>FKBP5 is a critical regulator of the stress response. Previous studies have shown that dysregulation of the expression of this gene plays a role in the pathogenesis of chronic pain development as well as a number of co-morbid neuropsychiatric disorders. In the current study, we identified a functional allele (rs3800373) in the 3'UTR of FKBP5 that influences vulnerability to chronic post-traumatic pain in two ethnic cohorts. Using multiple complimentary experimental approaches, we show that the FKBP5 rs3800373 minor allele alters the secondary structure of FKBP5 mRNA, decreasing the binding of a stress and pain associated microRNA, miR-320a. This results in relatively greater FKBP5 translation, unchecked by miR-320a, increasing glucocorticoid resistance and increasing vulnerability to post-traumatic pain.
546 ## - LANGUAGE NOTE
Language note English
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Chronic Pain/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *MicroRNAs/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Musculoskeletal Pain/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Tacrolimus Binding Proteins/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element 3' Untranslated Regions
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Topical term or geographic name entry element Adult
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Topical term or geographic name entry element African Americans/ge [Genetics]
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Topical term or geographic name entry element Alleles
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Topical term or geographic name entry element Chronic Pain/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element European Continental Ancestry Group/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Female
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Genotype
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Humans
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Male
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element MicroRNAs/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Musculoskeletal Pain/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Polymorphism, Single Nucleotide
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Protein Binding
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Protein Structure, Secondary
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Receptors, Glucocorticoid/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element RNA, Messenger/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Tacrolimus Binding Proteins/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Young Adult
651 ## - SUBJECT ADDED ENTRY--GEOGRAPHIC NAME
Institution MedStar Washington Hospital Center
656 ## - INDEX TERM--OCCUPATION
Department Emergency Medicine
657 ## - INDEX TERM--FUNCTION
Medline publication type Journal Article
700 ## - ADDED ENTRY--PERSONAL NAME
Local Authors Kaushik, Sangeeta
790 ## - Authors
All authors Datner E, Domeier R, Hendry PL, Kaushik S, Kurz MC, Kutchko KM, Lackey L, Laederach A, Lewandowski C, Linnstaedt SD, McCarthy KR, McLean SA, O'Neil B, Parker JS, Pearson C, Riker KD, Rueckeis CA, Tsai YH
856 ## - ELECTRONIC LOCATION AND ACCESS
DOI <a href="https://dx.doi.org/10.1523/JNEUROSCI.3458-17.2018">https://dx.doi.org/10.1523/JNEUROSCI.3458-17.2018</a>
Public note https://dx.doi.org/10.1523/JNEUROSCI.3458-17.2018
942 ## - ADDED ENTRY ELEMENTS (KOHA)
Koha item type Journal Article
Item type description Article
Holdings
Withdrawn status Lost status Damaged status Not for loan Collection Home library Current library Date acquired Total Checkouts Full call number Barcode Date last seen Price effective from Koha item type
          MedStar Authors Catalog MedStar Authors Catalog 08/31/2018   30150364 30150364 08/31/2018 08/31/2018 Journal Article

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