5′ untranslated regions: the next regulatory sequence in yeast synthetic biology

Published on Apr 1, 2020in Biological Reviews10.288
· DOI :10.1111/BRV.12575
Yatti De Nijs (UGent: Ghent University), Sofie De Maeseneire12
Estimated H-index: 12
(UGent: Ghent University),
Wim Soetaert38
Estimated H-index: 38
(UGent: Ghent University)
When developing industrial biotechnology processes, Saccharomyces cerevisiae (baker's yeast or brewer's yeast) is a popular choice as a microbial host. Many tools have been developed in the fields of synthetic biology and metabolic engineering to introduce heterologous pathways and tune their expression in yeast. Such tools mainly focus on controlling transcription, whereas post-transcriptional regulation is often overlooked. Herein we discuss regulatory elements found in the 5' untranslated region (UTR) and their influence on protein synthesis. We provide not only an overall picture, but also a set of design rules on how to engineer a 5' UTR. The reader is also referred to currently available models that allow gene expression to be tuned predictably using different 5' UTRs.
  • References (156)
  • Citations (0)
📖 Papers frequently viewed together
1 Author (Thomas Decoene)
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Haopeng Yu (NWAFU: Northwest A&F University)H-Index: 1
#2Wenjing Meng (NWAFU: Northwest A&F University)H-Index: 1
Last. Shiheng Tao (NWAFU: Northwest A&F University)H-Index: 1
view all 6 authors...
ABSTRACTThe structure of mRNA in vivo is unwound to some extent in response to multiple factors involved in the translation process, resulting in significant differences from the structure of the s...
1 CitationsSource
#1Seow Neng Chan (NUS: National University of Singapore)H-Index: 1
#2Jun Wei Pek (NUS: National University of Singapore)H-Index: 1
Intronic sequences are often regarded as ‘nonsense’ transcripts that are rapidly degraded. We highlight here recent studies on intronic sequences that play regulatory roles as long noncoding RNAs (lncRNAs) which are classified as sisRNAs. Interestingly, sisRNAs come in different forms and are produced via a variety of ways. They regulate genes at the DNA, RNA, and protein levels, and frequently engage in autoregulatory feedback loops to ensure cellular homeostasis under normal and stress conditi...
4 CitationsSource
#1Robert A. Crawford (MAHSC: Manchester Academic Health Science Centre)H-Index: 1
#2Graham D. Pavitt (MAHSC: Manchester Academic Health Science Centre)H-Index: 32
5 CitationsSource
#1Wentao Ding (CAS: Chinese Academy of Sciences)H-Index: 1
#2Jian Cheng (CAS: Chinese Academy of Sciences)H-Index: 2
Last. Huifeng Jiang (CAS: Chinese Academy of Sciences)H-Index: 12
view all 9 authors...
The 5′ untranslated region (5′UTR) plays a key role in post-transcriptional regulation, but interaction between nucleotides and directed evolution of 5′UTRs as synthetic regulatory elements remain unclear. By constructing a library of synthesized random 5′UTRs of 24 nucleotides in Saccharomyces cerevisiae, we observed strong epistatic interactions among bases from different positions in the 5′UTR. Taking into account these base interactions, we constructed a mathematical model to predict protein...
1 CitationsSource
#1Kathrin LeppekH-Index: 5
#2Rhiju DasH-Index: 46
Last. Maria BarnaH-Index: 24
view all 3 authors...
Structures in 5′ untranslated regions of eukaryotic mRNAs contribute to gene regulation by controlling cap-dependent and cap-independent translation initiation through diverse mechanisms. New structure probing technologies coupled with techniques such as compensatory mutagenesis will likely identify new structured RNA elements and help elucidate their function.
75 CitationsSource
19 CitationsSource
#1Florian Groher (Technische Universität Darmstadt)H-Index: 7
#2Cristina Bofill-Bosch (Technische Universität Darmstadt)H-Index: 2
Last. Beatrix Suess (Technische Universität Darmstadt)H-Index: 29
view all 8 authors...
RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswit...
9 CitationsSource
#1Thomas Decoene (UGent: Ghent University)H-Index: 2
#2Gert Peters (UGent: Ghent University)H-Index: 3
Last. Marjan De Mey (UGent: Ghent University)H-Index: 23
view all 4 authors...
Fine-tuning biosynthetic pathways is crucial for the development of economic feasible microbial cell factories. Therefore, the use of computational models able to predictably design regulatory sequences for pathway engineering proves to be a valuable tool, especially for modifying genes at the translational level. In this study we developed a computational approach for the de novo design of 5′-untranslated regions (5′UTRs) in Saccharomyces cerevisiae with a predictive outcome on translation init...
2 CitationsSource
#1Pieter Spealman (CMU: Carnegie Mellon University)H-Index: 2
#2Armaghan W. Naik (CMU: Carnegie Mellon University)H-Index: 7
Last. C. Joel McManus (CMU: Carnegie Mellon University)H-Index: 16
view all 7 authors...
15 CitationsSource
#1Josh T. Cuperus (UW: University of Washington)H-Index: 11
#2Benjamin Groves (UW: University of Washington)H-Index: 10
Last. Georg Seelig (UW: University of Washington)H-Index: 24
view all 7 authors...
Our ability to predict protein expression from DNA sequence alone remains poor, reflecting our limited understanding of cis-regulatory grammar and hampering the design of engineered genes for synthetic biology applications. Here, we generate a model that predicts the protein expression of the 5' untranslated region (UTR) of mRNAs in the yeast Saccharomyces cerevisiae. We constructed a library of half a million 50-nucleotide-long random 5' UTRs and assayed their activity in a massively parallel g...
40 CitationsSource
Cited By0