TY - JOUR
T1 - Biosynthesis of Circular RNA ciRS-7/CDR1as Is Mediated by Mammalian-wide Interspersed Repeats
AU - Yoshimoto, Rei
AU - Rahimi, Karim
AU - Hansen, Thomas B.
AU - Kjems, Jørgen
AU - Mayeda, Akila
N1 - Funding Information:
R.Y. was supported by a Research Grant from the Hori Sciences and Arts Foundation , a Research Grant from the Nitto Foundation , a Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan (PMAC), and Grants-in-Aid for Scientific Research (C) ( JP18K05563 ). A.M. was partly supported by Grants-in-Aid for Scientific Research (B) ( JP16H04705 ) and Grants-in-Aid for Challenging Exploratory Research ( JP16K14659 ) from the Japan Society for the Promotion of Science (JSPS). K.R. was supported by Villum Foundation .
Publisher Copyright:
© 2020 The Authors
PY - 2020/7/24
Y1 - 2020/7/24
N2 - Circular RNAs (circRNAs) are stable non-coding RNAs with a closed circular structure. One of the best studied circRNAs is ciRS-7 (CDR1as), which acts as a regulator of the microRNA miR-7; however, its biosynthetic pathway has remained an enigma. Here we delineate the biosynthetic pathway of ciRS-7. The back-splicing events that form circRNAs are often facilitated by flanking inverted repeats of the primate-specific Alu elements. The ciRS-7 gene lacks these elements, but, instead, we identified a set of flanking inverted elements belonging to the mammalian-wide interspersed repeat (MIR) family. Splicing reporter assays in HEK293 cells demonstrated that these inverted MIRs are required to generate ciRS-7 through back-splicing, and CRISPR/Cas9-mediated deletions confirmed the requirement of the endogenous MIR elements in SH-SY5Y cells. Using bioinformatic searches, we identified several other MIR-dependent circRNAs and confirmed them experimentally. We propose that MIR-mediated RNA circularization is used to generate a subset of mammalian circRNAs.
AB - Circular RNAs (circRNAs) are stable non-coding RNAs with a closed circular structure. One of the best studied circRNAs is ciRS-7 (CDR1as), which acts as a regulator of the microRNA miR-7; however, its biosynthetic pathway has remained an enigma. Here we delineate the biosynthetic pathway of ciRS-7. The back-splicing events that form circRNAs are often facilitated by flanking inverted repeats of the primate-specific Alu elements. The ciRS-7 gene lacks these elements, but, instead, we identified a set of flanking inverted elements belonging to the mammalian-wide interspersed repeat (MIR) family. Splicing reporter assays in HEK293 cells demonstrated that these inverted MIRs are required to generate ciRS-7 through back-splicing, and CRISPR/Cas9-mediated deletions confirmed the requirement of the endogenous MIR elements in SH-SY5Y cells. Using bioinformatic searches, we identified several other MIR-dependent circRNAs and confirmed them experimentally. We propose that MIR-mediated RNA circularization is used to generate a subset of mammalian circRNAs.
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U2 - 10.1016/j.isci.2020.101345
DO - 10.1016/j.isci.2020.101345
M3 - Article
AN - SCOPUS:85087992820
VL - 23
JO - iScience
JF - iScience
SN - 2589-0042
IS - 7
M1 - 101345
ER -