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Updated: Mar 15, 2026

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Mutual feedback regulation between Poly(A)-specific ribonuclease (PARN) and cognate microRNAs
Athanasios Kyritsis1, Rafailia Aa Beta1, Diana Scutelnic1
1Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Abstract:
The majority of pri-miRNAs acquire a 5' cap and 3' poly(A) tail. Mature miRNAs recruit deadenylases that shorten poly(Α) tails triggering target mRNA degradation. Poly(A)-specific ribonuclease (PARN) is a deadenylase that also mediates late steps of noncoding RNA maturation. Herein, we show that PARN affects the expression of a subset of miRNAs in NCI-H520 cells of lung cancer origin, including miR-29a and miR-1207, which are also predicted to target PARN mRNA. PARN associates with pri-miR-29a and pri-miR-1207 regulating their poly(A) lengths. Conversely, miR-29a-3p and miR-1207-5p bind the 3' UTR of PARN mRNA and regulate its expression. Cleavage and polyadenylation specificity factor 6 (CPSF6) recruits PARN to pri-miRNAs and together they affect primary and mature miR-29a-3p levels. Modulation of PARN, miR-29a-3p, or miR-1207-5p expression affects cell migration. We present a model to describe the dynamic relation between PARN and miR-29a and discuss its biological significance.
Insights
Poly(A)-specific ribonuclease (PARN) regulates microRNA (miRNA) expression by controlling poly(A) tail lengths of pri-miRNAs. This interaction impacts lung cancer cell migration, revealing a novel regulatory feedback loop.
Area of Science:
- Molecular Biology
- RNA Biology
- Cancer Biology
Background:
- Primary microRNAs (pri-miRNAs) are typically capped and polyadenylated.
- Mature miRNAs trigger mRNA degradation via deadenylases that shorten poly(A) tails.
- Poly(A)-specific ribonuclease (PARN) is a deadenylase involved in noncoding RNA maturation.
Purpose of the Study:
- To investigate the role of PARN in miRNA expression in lung cancer cells.
- To elucidate the regulatory relationship between PARN and specific miRNAs (miR-29a, miR-1207).
- To determine the impact of this interaction on lung cancer cell migration.
Main Methods:
- Analysis of PARN's association with pri-miR-29a and pri-miR-1207.
- Assessment of miR-29a and miR-1207 binding to PARN mRNA 3' UTR.
- Investigation of the role of Cleavage and polyadenylation specificity factor 6 (CPSF6) in recruiting PARN.
- Modulation of PARN, miR-29a, and miR-1207 expression to assess effects on cell migration.
Main Results:
- PARN associates with pri-miR-29a and pri-miR-1207, regulating their poly(A) tail lengths.
- miR-29a and miR-1207 bind to the 3' UTR of PARN mRNA, regulating its expression.
- CPSF6 facilitates PARN recruitment to pri-miRNAs, influencing miR-29a levels.
- Modulating PARN, miR-29a, or miR-1207 impacts lung cancer cell migration.
Conclusions:
- A dynamic feedback loop exists between PARN and miR-29a/miR-1207 in lung cancer cells.
- PARN and specific miRNAs regulate each other's expression and stability.
- This regulatory axis plays a significant role in lung cancer cell migration.
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