Circular RNA, the Key for Translation

Abstract

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m6A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m6A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

Circular RNA hsa_circ_0005567 overexpression promotes M2 type macrophage polarization through miR-492/SOCS2 axis to inhibit osteoarthritis progression

“…Circular RNAs (circRNAs) are non coding RNA molecules characterized by covalent closed loops free of 3' and 5' ends [10]. An increasing number of researches have suggested that novel circRNAs play various roles in osteoarthritis progression [11], such as CircCDH13 [12], circCSNK1G1 [13], circ_0128846 [14], etc.…”

CircN4bp1 Facilitates Sepsis-Induced Acute Respiratory Distress Syndrome Through Mediating Macrophage Polarization via the miR-138-5p/EZH2 Axis

“…Emerging evidence has suggested that m6A modi cation is a gene regulatory mechanism involved in the modulation of RNA stability, localization, splicing and translation [30] . However, the function and mechanism of m6A modi cation in ARDS have not yet been reported.…”

“…Interestingly, we observed the m6A level of circN4bp1 was unregulated in macrophages from ARDS mice model. It is well known that m6A modi cation is a dynamic and reversible process, including m6A writers (METTL3 and METTL14), erasers (FTO and ALKBH5) and readers (YTHDC1/2, YTHDF1/2/3 and IGF2BP1/2/3) [29,30] . We further found that METTL3, FTO and YTHDF2 were highly expressed in macrophages, among them the expression of METTL3 showed the most signi cant upregulation.…”

Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression

“… 158 Moreover, some circRNAs containing the AUG start codon and IRES can control gene expression at the translational level. 159 , 160 However, this effect has not yet been fully elucidated in cancer.…”