RNA polymerase III transcription-associated polyadenylation promotes the accumulation of noncoding retrotransposons during infection

• 成果类型: Article
• 署名作者: Lari, Azra; Shah, Sahil B.; Mao, Xiaowen; Sanghrajka, Priyanka; Karijolich, John; Lareau, Liana F.; Glaunsinger, Britt A.
• 署名单位: University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Vanderbilt University; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13778
• DOI: 10.1073/pnas.2507186122
• 发表日期: 2025-08-12
• 关键词: human alu elements; b2 rna; molecular-mechanisms; adenovirus type-5; pol ii; 3 end; activation; dna; expression; SEQUENCES

摘要

The accumulation of RNA Polymerase III (Pol III) transcribed short interspersed nuclear element (SINE) retrotransposon RNA is a hallmark of various cellular stressors, including DNA virus infection. However, the molecular mechanisms driving the induction of these normally repressed loci are largely undefined. Here, we reveal that in addition to Pol III transcriptional induction, gammaherpesvirus infection stimulates mRNA-like 3 ' end processing of SINE RNAs that leads to their stabilization. We developed a convolutional neural network (CNN)-based model that identified a polyadenylation-associated motif as the key hallmark of infection-induced SINEs. Indeed, mRNA polyadenylation machinery is recruited in a Pol III-dependent manner to virus-induced loci, including B2 SINE and tRNA genes. Infection causes enhanced polyadenylation of SINE ncRNA, which is required for its stable accumulation. This virus-host interaction therefore highlights an inducible, coupled relationship between Pol III transcription and mRNA-like polyadenylation. It also reveals that co-option of the polyadenylation machinery by Pol III is a mechanism to increase the abundance of noncoding RNA during pathogenic stress.