Nascent-chain biology
【Concept of Nascent-chain biology】Life depends on correct gene expressions. Proteins do not instantaneously finish the synthesis and folding into functioning products, but experience the nascent peptidyl-tRNAs, defined as “nascent chains”, during the translation. So far, nascent chains are regarded as transient intermediates during the protein synthesis. However, recent advances have revealed that nascent chains are directly involved in a variety of cellular processes including self-maturation and the quality control system of protein and mRNA. In addition, the dysfunction of the maturation and the quality control system could perturb cellular homeostasis, often leading to human diseases.
The concept of nascent chains joins the protein and RNA researchers to generate a new field called “Nascent-chain biology”. Our project aims to understand the roles of the “nascent chains” in the gene expression and cellular homeostasis.
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Below are our recent efforts on the nascent-chain biology.
【Nascent chain folding and the chaperone effects】 To understand the translation-coupled protein folding, we use a reconstituted cell-free translation system of E. coli (PURE system) and chaperones such as GroEL and DnaK (Hsp70 in E. coli).
【Selected publications】
-Niwa T, Uemura E, Matsuno Y, *Taguchi, H.
Translation-coupled protein folding assay using a protease to monitor the folding status.
Protein Science 28, 1252-1261 (2019) [Protein Science Best Paper award 2019]
-Uemura E, Niwa T, Minami S, Takemoto K, Fukuchi S, Machida K, Imataka H, Ueda T, Ota M, *Taguchi H.
Large-scale aggregation analysis of eukaryotic proteins reveals an involvement of intrinsically disordered regions in protein folding.
Sci Rep 8:678. (2018))
-Niwa, T, Kanamori T, *Ueda, T, *Taguchi H.
Global analysis of chaperone effects using a reconstituted cell-free translation system
Proc Natl Acad Sci USA 109, 8937-8942 (2012)
-Niwa, T., Ying, B.-W., Saito, K., Jin, W. Z., Takada, S., Ueda, T. *Taguchi, H.
Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of Escherichia coli proteins.
Proc Natl Acad Sci USA 106, 4201-4206 (2009)
【Noncanonical translation dynamics】We conducted a large-scale analysis of translatioal pausing. The study on the pausing led to the discovery of a novel noncanonical translation dynamics (Intrinsic ribosome destabilization: IRD), and we are currently working to explore the frontier of the protein world.
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【Selected publications】
-Chadani Y, Niwa T, Izumi T, Sugata N, Nagao A, Suzuki T, Chiba S, *Ito K, *Taguchi H.
Intrinsic ribosome destabilization underlies translation and provides an organism with a strategy of environmental sensing.
Mol Cell 68, 528-539 (2017)
-Chadani Y, Niwa T, Chiba S, *Taguchi H, *Ito K.
Integrated in vivo and in vitro nascent chain profiling reveals widespread translational pausing.
Proc Natl Acad Sci USA 113, E829-38 (2016)