title: Rolling Circle Translation of Circular RNA in Living Human Cells.
abstract: We recently reported that circular RNA is efficiently translated by a rolling circle amplification (RCA) mechanism in a cell-free Escherichia coli translation system. Recent studies have shown that circular RNAs composed of exonic sequences are abundant in human cells. However, whether these circular RNAs can be translated into proteins within cells remains unclear. In this study, we prepared circular RNAs with an infinite open reading frame and tested their translation in eukaryotic systems. Circular RNAs were translated into long proteins in rabbit reticulocyte lysate in the absence of any particular element for internal ribosome entry, a poly-A tail, or a cap structure. The translation systems in eukaryote can accept much simpler RNA as a template for protein synthesis by cyclisation. Here, we demonstrated that the circular RNA is efficiently translated in living human cells to produce abundant protein product by RCA mechanism. These findings suggest that translation of exonic circular RNAs present in human cells is more probable than previously thought.
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.|Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.|Nano Medical Engineering laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Abe
authors.affiliation: Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Nano Medical Engineering laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishihara
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.|Nano Medical Engineering laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Nano Medical Engineering laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.|Nano Medical Engineering laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shuto
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Nano Medical Engineering laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.|Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.|Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.|Nano Medical Engineering laboratory, RIKEN, 2-1 Hirosawa, Wako-Shi, Saitama 351-0198, Japan.|PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
mesh_terms: D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D014176:Protein Biosynthesis; D012313:RNA / Q000138:chemical synthesis; D000079962:RNA, Circular; D012333:RNA, Messenger; D011817:Rabbits
chemical_list: D000079962:RNA, Circular; D012333:RNA, Messenger; D012313:RNA