ArticlePLoS pathogens2016
Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- MicroRNA-122 as a diagnostic biomarker for hepatocellular carcinoma related to hepatitis C virus: a meta-analysis and systematic review.The Journal of international medical research · 2020Pooled it
- Standardized RNA extraction protocol forFrontiers in cellular and infection microbiology · 2026Article
- Regulation of viral hepatitis by N6-methyladenosine RNA methylation.Emerging microbes & infections · 2025Review
- Role of the epitranscriptome in viral infections: beneficial or detrimental?Memorias do Instituto Oswaldo Cruz · 2025Review
- METTL14 Induced NJournal of Cancer · 2024Article
- AntiVIRmiR: A repository of host antiviral miRNAs and their expression along with experimentally validated viral miRNAs and their targets.Frontiers in genetics · 2022Article
- Value of Serum miRNA-96-5p and miRNA-99a-5p as Diagnostic Biomarkers for Hepatocellular Carcinoma.International journal of general medicine · 2022Article
- Gld2 activity and RNA specificity is dynamically regulated by phosphorylation and interaction with QKI-7.RNA biology · 2021Article
- Review
- Regulation of RNA stability at the 3' end.Biological chemistry · 2021Review
- Functions and mechanisms of RNA tailing by metazoan terminal nucleotidyltransferases.Wiley interdisciplinary reviews. RNA · 2021Review
- The role of N6-methyladenosine modification in the life cycle and disease pathogenesis of hepatitis B and C viruses.Experimental & molecular medicine · 2021Review
- Article
- The Significance of HCV Viral Load in the Incidence of HCC: a Correlation Between Mir-122 and CCL2.Journal of gastrointestinal cancer · 2020Review
- Merkel cell polyomavirus oncoproteins induce microRNAs that suppress multiple autophagy genes.International journal of cancer · 2020Article
- The RNA-binding protein QKI-7 recruits the poly(A) polymerase GLD-2 for 3' adenylation and selective stabilization of microRNA-122.The Journal of biological chemistry · 2020Article
- Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments.Nucleic acids research · 2019Article
- Gld2 activity is regulated by phosphorylation in the N-terminal domain.RNA biology · 2019Article
- Identifying and characterizing functional 3' nucleotide addition in the miRNA pathway.Methods (San Diego, Calif.) · 2019Review
- Vibrio vulnificus quorum-sensing molecule cyclo(Phe-Pro) inhibits RIG-I-mediated antiviral innate immunity.Nature communications · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3' end by 3'-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3'-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3' end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.