《生命科学》 2026, 38(9): 1620-1633

内含子保留与3’非翻译区延长介导的信使RNA核滞留

蒋清怡^1,2 , 程 红^1,3,*

¹中国科学院分子细胞科学卓越创新中心，上海 200031 ²中国科学院大学，北京 100049 ³国科大杭州高等研究院生命与健康科学学院，杭州 310024

摘　要：

在真核细胞中，信使RNA（messenger RNA，mRNA）的出核转运是基因表达的关键步骤。新生mRNA前体只有在细胞核内完成剪接、3’端加工等步骤后才能被运输出核，在细胞质中被翻译成蛋白质。mRNA加工过程往往会影响其出核转运，其中内含子保留（intron retention，IR）及3’非翻译区（untranslated region，UTR）延长是导致mRNA核滞留的重要因素。本综述阐述了两者介导mRNA核滞留的分子机制及其相关生理、病理功能，并探讨了两者的协同调控，以期为理解mRNA核滞留如何调控基因表达提供见解。

通讯作者：程 红 , Email:hcheng@sibcb.ac.cn

Intron retention and 3’UTR lengthening mediate mRNA nuclear retention

JIANG Qing-Yi^1,2 , CHENG Hong^1,3,*

¹Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China ²University of Chinese Academy of Sciences, Beijing 100049, China ³School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China

Abstract:

In eukaryotic cells, the export of messenger RNA from the nucleus to the cytoplasm is a critical step in gene expression. This process is tightly linked to pre-mRNA processing, such as splicing and 3’end maturation, which act as checkpoints for export. While most mRNAs are exported rapidly after processing, certain transcripts are held back in the  nucleus, a phenomenon known as mRNA nuclear retention. Once thought to be a side-effect in RNA processing,  nuclear retention is now recognized as a deliberate and sophisticated gene regulatory mechanism. Two major factors driving this process are intron retention and the lengthening of 3’ UTR. This review explores how these two events determine mRNA nuclear retention. First, current research underscores introns as strong gatekeepers of mRNA nuclear export. Specifically, retained introns prevent mRNAs from leaving the nucleus. These transcripts are either degraded by nuclear quality control or stored as a stable “nuclear reservoir”. When the cell encounters stress or external stimuli, these retained RNAs can be rapidly spliced and exported to produce proteins. This allows the cell to respond much faster than by starting new transcription. However, if this retention fails, escaped IR transcripts can lead to the production of abnormal proteins, contributing to diseases like cancer and neurodegeneration. Beyond introns, long 3’ UTRs produced from alternative polyadenylation (APA) provide additional docking sites for retention factors. Compared to shorter versions, long 3’ UTRs often contain specific sequences or structures that promote nuclear retention. These elements recruit protein factors that anchor the mRNA within nuclear bodies such as paraspeckles. On the other hand, chemical modifications on long 3’ UTRs can limitedly buffer this retention by dynamically regulating the binding of export factors. Finally, we discuss how intron retention and 3’ UTR lengthening can cooperate to enhance the nuclear retention of mRNAs. Understanding such mechanisms will reveal how cells use nuclear compartmentalization to maintain transcriptome plasticity and respond to physiological and pathological changes.

Communication Author：CHENG Hong , Email:hcheng@sibcb.ac.cn