TY - JOUR
T1 - Quaking regulates circular RNA production in cardiomyocytes
AU - Montanes-Agudo, Pablo
AU - van der Made, Ingeborg
AU - Aufiero, Simona
AU - Tijsen, Anke J.
AU - Pinto, Yigal M.
AU - Creemers, Esther E.
N1 - Funding Information: We would like to express our gratitude to the Animal Research Institute AMC for their labor in animal husbandry, as well as to the Core Facility Genomics of the Amsterdam UMC for conducting the RNA-sequencing used in our study. This work was supported by grants from the Rembrandt Institute of Cardiovascular Science (2017) to E.E.C. and from the Netherlands Cardiovascular Research Initiative CVON (CVON-ARENA-PRIME) to Y.M.P. Open Access funding provided by University of Amsterdam. Deposited in PMC for immediate release. Funding Information: This work was supported by grants from the Rembrandt Institute of Cardiovascular Science (2017) to E.E.C. and from the Netherlands Cardiovascular Research Initiative CVON (CVON-ARENA-PRIME) to Y.M.P. Open Access funding provided by University of Amsterdam. Deposited in PMC for immediate release. Publisher Copyright: © 2023 Company of Biologists Ltd. All rights reserved.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Circular RNAs (circRNAs) are a class of non-coding RNA molecules that are gaining increasing attention for their roles in various pathophysiological processes. The RNA-binding protein quaking (QKI) has been identified as a regulator of circRNA formation. In this study, we investigate the role of QKI in the formation of circRNAs in the heart by performing RNA-sequencing on Qki-knockout mice. Loss of QKI resulted in the differential expression of 17% of the circRNAs in adult mouse hearts. Interestingly, the majority of the QKI-regulated circRNAs (58%) were derived from genes undergoing QKI-dependent splicing, indicating a relationship between back-splicing and linear splicing. We compared these QKI-dependent circRNAs with those regulated by RBM20, another cardiac splicing factor essential for circRNA formation. We found that QKI and RBM20 regulate the formation of a distinct, but partially overlapping set of circRNAs in the heart. Strikingly, many shared circRNAs were derived from the Ttn gene, and they were regulated in an opposite manner. Our findings indicate that QKI not only regulates alternative splicing in the heart but also the formation of circRNAs.
AB - Circular RNAs (circRNAs) are a class of non-coding RNA molecules that are gaining increasing attention for their roles in various pathophysiological processes. The RNA-binding protein quaking (QKI) has been identified as a regulator of circRNA formation. In this study, we investigate the role of QKI in the formation of circRNAs in the heart by performing RNA-sequencing on Qki-knockout mice. Loss of QKI resulted in the differential expression of 17% of the circRNAs in adult mouse hearts. Interestingly, the majority of the QKI-regulated circRNAs (58%) were derived from genes undergoing QKI-dependent splicing, indicating a relationship between back-splicing and linear splicing. We compared these QKI-dependent circRNAs with those regulated by RBM20, another cardiac splicing factor essential for circRNA formation. We found that QKI and RBM20 regulate the formation of a distinct, but partially overlapping set of circRNAs in the heart. Strikingly, many shared circRNAs were derived from the Ttn gene, and they were regulated in an opposite manner. Our findings indicate that QKI not only regulates alternative splicing in the heart but also the formation of circRNAs.
KW - Alternative splicing
KW - Cardiomyocytes
KW - Quaking
KW - RNA-binding proteins
KW - circRNAs
UR - http://www.scopus.com/inward/record.url?scp=85169061942&partnerID=8YFLogxK
U2 - https://doi.org/10.1242/jcs.261120
DO - https://doi.org/10.1242/jcs.261120
M3 - Article
C2 - 37272356
SN - 0021-9533
VL - 136
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 13
M1 - jcs261120
ER -