دورية أكاديمية

Differential Stability of miR-9-5p and miR-9-3p in the Brain Is Determined by Their Unique Cis - and Trans -Acting Elements.

التفاصيل البيبلوغرافية
العنوان: Differential Stability of miR-9-5p and miR-9-3p in the Brain Is Determined by Their Unique Cis - and Trans -Acting Elements.
المؤلفون: Kim CK; Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153 ckim9@luc.edu., Asimes A; Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153., Zhang M; Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153., Son BT; Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153., Kirk JA; Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153., Pak TR; Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153.
المصدر: ENeuro [eNeuro] 2020 Jun 11; Vol. 7 (3). Date of Electronic Publication: 2020 Jun 11 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 101647362 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2373-2822 (Electronic) Linking ISSN: 23732822 NLM ISO Abbreviation: eNeuro Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Washington, DC] : Society for Neuroscience, [2014]-
مواضيع طبية MeSH: MicroRNAs*/genetics, Base Sequence ; Brain
مستخلص: microRNAs (miRs) are fundamental regulators of protein coding genes. In the CNS, miR-9 is highly enriched and critical for neuronal development and function. Mature miRs are derived from a duplex precursor, and the -5p strand ("guide") is preferentially incorporated into an RNA-induced silencing complex (RISC) to exert its regulatory functions, while the complementary -3p strand ("passenger") is thought to be rapidly degraded. By contrast, both strands of the miR-9 duplex have unique functions critical for neuronal physiology, yet their respective degradation rates and mechanisms governing degradation are not well understood. Therefore, we determined the degradation kinetics of miR-9-5p and miR-9-3p and investigated the cis and trans elements that affected their stability in the brain. Using a combination of homogeneous neuronal/astrocyte cell models and heterogeneous brain tissue lysate, we demonstrate the novel finding that miR-9-3p was more stable than the miR-9-5p guide strand in all models tested. Moreover, the degradation kinetics of both miR-9-5p and miR-9-3p were brain-region specific, suggesting that each brain region was differentially enriched for specific degradation factors. We also determined that the 3' nucleotides harbor important cis elements required to not only maintain stability, but also to recruit potential protein degradation factors. We used mass spectrometry to assess the miR-9 interacting proteins and found that the -5p and -3p strands were associated with functionally distinct proteins. Overall, these studies revealed unique miR-9-5p and miR-9-3p degradation kinetics in the brain and proposed critical nucleotide sequences and protein partners that could contribute to this differential stability.
(Copyright © 2020 Kim et al.)
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معلومات مُعتمدة: R01 AG033605 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: degradation; hippocampus; hypothalamus; microRNA; rat; stability
المشرفين على المادة: 0 (MicroRNAs)
تواريخ الأحداث: Date Created: 20200508 Date Completed: 20210618 Latest Revision: 20230215
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7294468
DOI: 10.1523/ENEURO.0094-20.2020
PMID: 32376600
قاعدة البيانات: MEDLINE
الوصف
تدمد:2373-2822
DOI:10.1523/ENEURO.0094-20.2020