Academic Journal
Evaluation of synthetic post-transcription regulatory sequences reveals design principle to enhance mRNA stability and translation efficiency.
| Τίτλος: | Evaluation of synthetic post-transcription regulatory sequences reveals design principle to enhance mRNA stability and translation efficiency. |
|---|---|
| Συγγραφείς: | Zhang JP; School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, 214122, PR China., Mei ZL; School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, 214122, PR China., Ren JW; School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, 214122, PR China.; National Engineering Research Center for Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, PR China., Zhang XM; School of Life Science and Health Engineering, Jiangnan University, Wuxi, 214122, PR China., Gong JS; School of Life Science and Health Engineering, Jiangnan University, Wuxi, 214122, PR China., Xu GQ; School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, 214122, PR China.; National Engineering Research Center for Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, PR China., Li H; School of Life Science and Health Engineering, Jiangnan University, Wuxi, 214122, PR China., Zhang XJ; School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, 214122, PR China.; National Engineering Research Center for Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, PR China., Xu ZH; School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi, 214122, PR China.; College of Biomass Science and Engineering, Sichuan University, 24 Southern Yihuan, Chengdu, 610065, PR China. |
| Πηγή: | Synthetic and systems biotechnology [Synth Syst Biotechnol] 2025 Dec 08; Vol. 12, pp. 160-171. Date of Electronic Publication: 2025 Dec 08 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: KeAi Communications Co Country of Publication: China NLM ID: 101694371 Publication Model: eCollection Cited Medium: Internet ISSN: 2405-805X (Electronic) Linking ISSN: 2405805X NLM ISO Abbreviation: Synth Syst Biotechnol Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [Beijing, China] : KeAi Communications Co., [2016]- |
| Περίληψη: | The Shine-Dalgarno (SD) sequence and its adjacent flanking regions, including the translation standby site (TSS) and the N-terminal coding sequence (NCS), play critical roles in regulating ribosome recruitment, translation efficiency, and mRNA stability against RNase degradation. However, structure-activity relationships governing these regions remain poorly characterized, and their functional interplay introduces substantial complexity. In this study, we employed one-pot technology to build a post-transcriptional regulatory component (PTRC) library of 576 variants to clarify the relationship between sequence variants and both protein expression and mRNA levels via high-throughput sequencing. Our results show that although unstructured TSSs do not enhance mRNA stability, they markedly increase translation efficiency, causing a 16 %-100 % rise in protein expression. In contrast, structured TSSs increase mRNA levels by 43 %-90 %. Additionally, highly conserved SD sequences boost translation efficiency by up to 10 % and mRNA abundance by up to 12 %. Moreover, it was found that optimized linear N-terminal coding sequence (NCS) positively affects protein expression and mRNA levels. The effects of these optimized regulatory components were verified in the expression control of the nrk and sam2 genes, resulting in enhanced production. These findings underscore the crucial role of structural optimization, guiding the rational design of synthetic post-transcriptional regulatory elements. (© 2025 The Authors.) |
| Competing Interests: | The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
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| Contributed Indexing: | Keywords: 5′ mRNA; Transcript abundance; Translation efficiency |
| Entry Date(s): | Date Created: 20251229 Date Completed: 20251229 Latest Revision: 20260926 |
| Update Code: | 20260926 |
| PubMed Central ID: | PMC12743556 |
| DOI: | 10.1016/j.synbio.2025.11.011 |
| PMID: | 41459189 |
| Βάση Δεδομένων: | MEDLINE |
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