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 |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Adult |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
African Americans/ge [Genetics] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Alleles |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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 |