# Mutual feedback regulation between Poly(A)-specific ribonuclease (PARN) and cognate microRNAs

## TL;DR

This study reveals a mutual feedback loop between PARN and specific microRNAs, showing how they regulate each other's expression and affect cell migration.

## Contribution

The paper identifies a novel dynamic feedback mechanism between PARN and miR-29a/miR-1207, mediated by CPSF6.

## Key findings

- PARN regulates the poly(A) lengths of pri-miR-29a and pri-miR-1207.
- miR-29a-3p and miR-1207-5p target PARN mRNA, forming a feedback loop.
- CPSF6 recruits PARN to pri-miRNAs, influencing miRNA levels and cell migration.

## Abstract

PARN regulates poly(A) lengths of pri-miR-29a and pri-miR-1207, which in turn target PARN mRNA. CPSF6 recruits PARN to pri-miRNAs, modulating miRNA levels and cell migration, revealing a dynamic mutual feedback between PARN and specific microRNAs.

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.