Circular RNAs’ cap-independent translation protein and its roles in carcinomas

Abstract

Circular RNAs a kind of covalently closed RNA and widely expressed in eukaryotes. CircRNAs are involved in a variety of physiological and pathological processes, but their regulatory mechanisms are not fully understood. Given the development of the RNA deep-sequencing technology and the improvement of algorithms, some CircRNAs are discovered to encode proteins through the cap-independent mechanism and participate in the important process of tumorigenesis and development. Based on an overview of CircRNAs, this paper summarizes its translation mechanism and research methods, and reviews the research progress of CircRNAs translation in the field of oncology in recent years. Moreover, this paper aims to provide new ideas for tumor diagnosis and treatment through CircRNAs translation.

Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency

“…Adding poly(A) tails lowers mRNA immunogenicity by lowering U content and shielding mRNA in the sequence. The reduced efficacy of protein expression produced by high GC concentration needs to be addressed (Wang et al 2021 ). mRNA purification is also required after IVT to eliminate immunogenicity.…”

“…Most vaccines are derived from antiviral immunity (Rabinovich et al 1994 ). At present, various virus-specific vaccines are administered for routine vaccination, resulting in substantial advancements in the prevention and treatment of viral illnesses (Wang et al 2021 ). The first report of the successful use of in vitro transcribed (IVT) mRNA in animals was reported in 1990 (Pardi et al 2018 ).…”

“…It is widely expected that the efficiency of an mRNA vaccination would increase as protein expression is extended; therefore, improved mRNA vaccines will emerge from improved mRNA formats. mRNA vaccines are a promising vaccine candidates against the pandemic due to their short production time, economical, variety in vaccine construct, and clinically validated ability to stimulate cellular and humoral immune responses (Wang et al 2021 ; Verbeke et al 2021 ). This review discussed the iterative optimization and significant modifications of the mRNA structure particularly the 5′ cap, 5′ and 3′UTRs, the coding region, and the poly(A) tail which improve the stability, translation capacity and increase the efficacy of mRNA vaccines to trigger the immune response.…”

Research Progress of circRNAs in Glioblastoma

“…Normally circRNAs cannot be flipped, but with deeper research, it was found that exon sequences of some circRNAs can be translated into proteins ( Chen and Shan, 2021 ; Dodbele et al, 2021 ). Some circRNAs contain internal ribosome entry site (IRES) sequences and can bind directly to ribosomes and can be translated in eukaryotic cells ( Abe et al, 2015 ; He L. et al, 2021 ). The 40S subunit of eukaryotic ribosomes binds to circRNAs and can directly initiate translation ( Wang and Wang, 2015 ).…”

Research Progress on Circular RNA in Glioma

“…Notably, circRNA could also translate proteins through rolling circle amplification (RCA) mechanism. To be specifically, the number of nucleotide of these circRNAs is multiple of three and they only have start codons but lack of stop codons, which theoretically means high-molecular weight proteins could be produced once translation begins ( 106 ) ( Figure 2D ).…”