Interferon-alpha competing endogenous RNA network antagonizes microRNA-1270.

Cell Mol Life Sci

Department of Pharmacy, Laboratory of Microbiology and Cell Biology, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan,

Published: July 2015

AI Article Synopsis

  • Researchers have discovered a new type of gene regulation where RNAs interact and compete for the same microRNAs (miRNAs), forming a network called competing endogenous RNAs (ceRNAs) that can inhibit miRNA activity.
  • A specific antisense RNA (AS) related to interferon-α1 (IFN-α1) regulates its own stability by forming a ceRNA network with other IFN-α subtypes, thus affecting the levels of IFN-α1 mRNA by targeting miRNA-1270 (miR-1270).
  • Bioinformatics and experimental analysis show that the IFN-α1 AS contains multiple binding sites for miR-1270 and interacts with other RNA subtypes, revealing an

Article Abstract

A new form of circuitry for gene regulation has been identified in which RNAs can crosstalk by competing for shared microRNAs (miRNAs). Such competing endogenous RNAs (ceRNAs) form a network via shared miRNA response elements (MREs) to antagonize miRNA function. We previously reported natural antisense RNA (AS) as an important modulator of interferon-α1 (IFN-α1) mRNA levels by promoting IFN-α1 mRNA stability. We show that IFN-α1 AS forms a ceRNA network with specific IFN-α AS (IFN-α7/-α8/-α10/-α14) and mRNA (IFN-α8/-α10/-α14/-α17) subtypes from the IFN-α gene (IFNA) family to antagonize miRNA-1270 (miR-1270), thereby modulating IFN-α1 mRNA levels. Bioinformatic analysis demonstrated that IFN-α1 AS harbors multiple miR-1270 MREs (MRE-1270s), whose presence was substantiated by miR-1270 overexpression and transfection of antimiR-1270. The antimiR-1270, complementary to the miR-1270 seed region, revealed that IFN-α1 AS likely shares the MRE-1270 with IFN-α1 mRNA and specific IFN-α AS and mRNA subtypes. Subsequent bioinformatic analysis for MRE-1270s showed that IFN-α1 AS and other RNA subtypes shared the 6-mer MRE-1270 site. Further MRE-mapping demonstrated that the total number of MRE-1270s in IFN-α1 AS accounted for approximately 30 % of the miR-1270 population. AntimiR-1270 transfection also caused specific de-repression of five cellular mRNAs, including that of CAPRIN1. These results suggest that IFN-α1 AS, together with specific IFN-α AS and mRNA subtypes, as well as the five cellular mRNAs, participate as competing molecules in the ceRNA network against miR-1270. This coordinated regulatory architecture suggests a vital function for the innate immune system in maintaining precise physiological type I IFN levels via post-transcriptional regulatory mechanisms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477080PMC
http://dx.doi.org/10.1007/s00018-015-1875-5DOI Listing

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