Protein solubility and folding enhancement by interaction with RNA.
While basic mechanisms of several major molecular chaperones are well understood, this machinery has been known to be involved in folding of only limited number of proteins inside the cells. Here, we report a chaperone type of protein folding facilitated by interaction with RNA. When an RNA-binding module is placed at the N-terminus of aggregation-prone target proteins, this module, upon binding with RNA, further promotes the solubility of passenger proteins, potentially leading to enhancement of proper protein folding. Studies on in vitro refolding in the presence of RNA, coexpression of RNA molecules in vivo and the mutants with impaired RNA binding ability suggests that RNA can exert chaperoning effect on their bound proteins. The results suggest that RNA binding could affect the overall kinetic network of protein folding pathway in favor of productive folding over off-pathway aggregation. In addition, the RNA binding-mediated solubility enhancement is extremely robust for increasing soluble yield of passenger proteins and could be usefully implemented for high-throughput protein expression for functional and structural genomic research initiatives. The RNA-mediated chaperone type presented here would give new insights into de novo folding in vivo.
Choi
Seong Il
SI
Institute of Life Science and Biotechnology, Yonsei University, Seodaemun-Gu, Seoul, Korea.
Han
Kyoung Sim
KS
Kim
Chul Woo
CW
Ryu
Ki-Sun
KS
Kim
Byung Hee
BH
Kim
Kyun-Hwan
KH
Kim
Seo-Il
SI
Kang
Tae Hyun
TH
Shin
Hang-Cheol
HC
Lim
Keo-Heun
KH
Kim
Hyo Kyung
HK
Hyun
Jeong-Min
JM
Seong
Baik L
BL
D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004742:Enhancer Elements, Genetic; D006801:Humans; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D012995:Solubility
D018832:Molecular Chaperones; D011506:Proteins; D012313:RNA; D004247:DNA