Year: 2025
Type: article
Abstract: MicroRNAs (miRNAs) interact with the target mRNAs to induce translational repression and mRNA degradation. Interestingly, miRNAs themselves can turnover rapidly when binding to a target RNA with extensive complementarity, a phenomenon called target-directed miRNA degradation (TDMD). To date, all validated TDMD “triggers” can induce miRNA degradation reside in non-coding regions of the RNA. We found that TDMD triggers placed in the 3′ untranslated region (UTR) of a reporter degraded miRNAs more effectively than those in the coding sequence (CDS). Inhibiting translation of the reporter enhanced miRNA degradation by the CDS trigger, indicating that ribosome-free CDS triggers are more accessible to miRNAs. By small RNA sequencing, we explored mammalian miRNAs sensitive to global translation status. Yet, no endogenous CDS trigger could be confidently assigned to these miRNAs. Our work revealed the intricate relationship between translation and TDMD, and explains the paucity of effective TDMD triggers in the CDS. Stable microRNAs (miRNAs) can undergo turnover via target-directed miRNA degradation (TDMD). Here, the authors show that TDMD triggers in non-coding regions degrade miRNAs more effectively than those in coding regions, where translation interferes with this process.
Source: Nature Communications
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, American Cancer Society, National Institutes of Health, Japan Science and Technology Agency, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Advancing Drug Repositioning for Alzheimer’s Disease using Real-world Data, Post-Acute Sequelae of SARS-CoV-2 Infection and Subsequent Disease Progression in Individuals with AD/ADRD: Influence of the Social and Environmental Determinants of Health, G2654747551, G3075388561, タンパク質合成の時空間制御から見た多細胞システムの理解, G3427963090, G5062585832, G5319896519, MicroRNA turnover induced by target RNAs in colorectal cancer, G9000079008, G9000319873, An end-to-end informatics framework to study Multiple Chronic Conditions (MCC)'s impact on Alzheimer's disease using harmonized electronic health records, Exploring microRNA degradation in T-cell acute lymphoblastic leukemia, Basic Microbiology and Infectious Disease, Molecular mechanisms for regulating microRNA levels in metazoans, G982581970
OpenAlex ID: W4411085307