NAR | A Side Story of Ribosomal Pausing: How Boron Responsiveness in Plants is Regulated by NIP5;1

Introduction

In eukaryotes, gene expression involves multiple cellular compartments. After DNA transcription in the cell nucleus, pre-mRNA undergoes capping, splicing, 3' truncation, and poly(A) addition to form mature mRNA, which is then translated in the cytoplasm after nuclear export. mRNA stability is regulated by the 5' or 3' UTR; for example, uORFs on the 5' UTR can induce mRNA degradation through ribosome stalling, while simultaneously reducing the translation of the main ORF.

Transcription and mRNA degradation were once considered independent processes, but recent studies have shown that they are subject to feedback regulation:

A) Studies in zebrafish and mice found that nonsense-mediated mRNA decay (NMD), triggered by premature termination codons (PTCs), can upregulate the transcription of functionally related genes. mRNA fragments may trigger a genetic compensation response via chromatin modification.

B) Yeast studies have shown that mutations in mRNA degradation factors increase mRNA stability but do not affect their steady-state levels, indicating that changes in mRNA half-life can be counterbalanced by reverse transcriptional regulation.

Boron (B) is an essential nutrient for plant growth but becomes toxic when present in excess. NIP5;1 functions as a boric acid transporter, promoting absorption under low boron conditions, whereas its mRNA becomes unstable under high boron conditions to prevent excessive uptake. This degradation is triggered by AUGUAA-induced ribosome stalling on the 5'UTR. Boron stabilizes eRF1 and promotes its interaction with Met-tRNAi, hindering translation reinitiation and leading to mRNA cleavage and degradation. Additionally, NIP5;1 expression is regulated by STOP1, although no response to boron has been observed. The transcriptional regulatory mechanism of NIP5;1 in response to boron remains to be elucidated.

On March 24, 2025, the research team led by Toru Fujiwara at the Institute of Agricultural and Life Sciences, University of Tokyo, published a paper titled "Ribosome stalling-induced NIP5;1 mRNA decay triggers ARGONAUTE1-dependent transcription downregulation" in Nucleic Acids Research. They proposed a novel regulatory model wherein the translational process not only senses nutrient status to selectively degrade mRNA and reduce translation, but also utilizes this degradation process together with AGO1 as a triggering signal to induce transcriptional downregulation. These processes are intricately intertwined, forming a multilayered coupling between transcription, mRNA degradation, and translation, enabling highly precise regulation and rapid responses to environmental changes.