Biosynthesis of Circular RNA ciRS-7/CDR1as Is Mediated by Mammalian-wide Interspersed Repeats

IScience
Rei YoshimotoAkila Mayeda

Abstract

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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Citations

Dec 16, 2020·Molecular Cancer·Wei-Yi ZhouRui-Hua Xu
Feb 26, 2021·EMBO Reports·Samantha DodbeleJeremy E Wilusz
Mar 23, 2021·Frontiers in Cell and Developmental Biology·Zhenguo YangQingyun Chen
Apr 4, 2021·Cancers·Patrizia BonelliMaria Lina Tornesello
Apr 23, 2021·Wiley Interdisciplinary Reviews. RNA·John G Conboy
Jun 13, 2021·Ageing Research Reviews·Yang YangYe Tian
Jul 20, 2021·Frontiers in Microbiology·Takanobu TagawaJoseph M Ziegelbauer
Jul 20, 2021·Neurochemistry International·Suresh L MehtaRaghu Vemuganti
Aug 1, 2021·Oncogene·Nicol MecozziFlorian A Karreth
Sep 28, 2021·Methods : a Companion to Methods in Enzymology·Karim RahimiJørgen Kjems

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Methods Mentioned

BETA
RNA-seq
antisense oligoribonucleotides
transfection
PCR
electrophoresis

Software Mentioned

RepeatMasker
RNAup
UCSC Genome Browser

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