PMID- 30525473
OWN - NLM
STAT- MEDLINE
DCOM- 20191008
LR  - 20191008
IS  - 2161-5063 (Electronic)
IS  - 2161-5063 (Linking)
VI  - 7
IP  - 12
DP  - 2018 Dec 21
TI  - Engineering the 5' UTR-Mediated Regulation of Protein Abundance in Yeast Using 
      Nucleotide Sequence Activity Relationships.
PG  - 2709-2714
LID - 10.1021/acssynbio.8b00127 [doi]
AB  - 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 abundance with a precision of R(2) = 0.60. 
      On the basis of this model, we developed an approach to engineer 5'UTRs according 
      to nucleotide sequence activity relationships (NuSAR), in which 5'UTRs were 
      engineered stepwise through repeated cycles of backbone design, directed 
      screening, and model reconstruction. After three rounds of NuSAR, the predictive 
      accuracy of our model was improved to R(2) = 0.71, and a strong 5'UTR was 
      obtained with 5-fold higher protein abundance than the starting 5'UTR. Our 
      findings provide new insights into the mechanism of 5'UTR regulation and 
       contribute to a new translational elements engineering approach in synthetic 
      biology.
FAU - Ding, Wentao
AU  - Ding W
AD  - Key Laboratory of Systems Microbial Biotechnology , Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences , Tianjin 300308 , China.
AD  - Beijing Advanced Innovation Center for Soft Matter Science and Engineering , 
      Beijing University of Chemical Technology , Beijing 100029 , China.
FAU - Cheng, Jian
AU  - Cheng J
AD  - Key Laboratory of Systems Microbial Biotechnology , Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences , Tianjin 300308 , China.
FAU - Guo, Dan
AU  - Guo D
AD  - Key Laboratory of Systems Microbial Biotechnology , Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences , Tianjin 300308 , China.
FAU - Mao, Ling
AU  - Mao L
AD  - College of Biology and Pharmaceutical Engineering , Wuhan Polytechnic University 
      , Wuhan 430023 , China.
FAU - Li, Jingwei
AU  - Li J
AD  - Laboratory of Mathematics for Nonlinear Science, Shanghai Key Laboratory for 
      Contemporary Applied Mathematics, Centre for Computational Systems Biology, 
      School of Mathematical Sciences , Fudan University , Shanghai 200433 , China.
FAU - Lu, Lina
AU  - Lu L
AD  - Key Laboratory of Systems Microbial Biotechnology , Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences , Tianjin 300308 , China.
FAU - Zhang, Yunxin
AU  - Zhang Y
AD  - Laboratory of Mathematics for Nonlinear Science, Shanghai Key Laboratory for 
      Contemporary Applied Mathematics, Centre for Computational Systems Biology, 
      School of Mathematical Sciences , Fudan University , Shanghai 200433 , China.
FAU - Yang, Jiangke
AU  - Yang J
AD  - College of Biology and Pharmaceutical Engineering , Wuhan Polytechnic University 
      , Wuhan 430023 , China.
FAU - Jiang, Huifeng
AU  - Jiang H
AUID- ORCID: 0000-0002-3757-7896
AD  - Key Laboratory of Systems Microbial Biotechnology , Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences , Tianjin 300308 , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181213
PL  - United States
TA  - ACS Synth Biol
JT  - ACS synthetic biology
JID - 101575075
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Oligonucleotides)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Base Sequence
MH  - Directed Molecular Evolution
MH  - Genetic Engineering/*methods
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Models, Theoretical
MH  - Oligonucleotides/genetics/*metabolism
MH  - Plasmids/genetics/metabolism
MH  - Regulatory Sequences, Nucleic Acid
MH  - Saccharomyces cerevisiae/genetics/*metabolism
OTO - NOTNLM
OT  - 5' untranslated region
OT  - Saccharomyces cerevisiae
OT  - directed evolution
OT  - translational regulation
EDAT- 2018/12/12 06:00
MHDA- 2019/10/09 06:00
CRDT- 2018/12/12 06:00
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2019/10/09 06:00 [medline]
PHST- 2018/12/12 06:00 [entrez]
AID - 10.1021/acssynbio.8b00127 [doi]
PST - ppublish
SO  - ACS Synth Biol. 2018 Dec 21;7(12):2709-2714. doi: 10.1021/acssynbio.8b00127. Epub 
      2018 Dec 13.