CircRNA and lncRNA-encoded peptide in diseases, an update review

Abstract

Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.

Keywords: Diagnosis; Molecular mechanisms; Non-coding RNAs; Peptide encoding; Targeted therapy; Tumorigenesis.

Fig. 1

Translation mechanism of lncRNAs and circRNAs. (A) Certain non-coding RNAs possess open reading frames and internal ribosome entry site sequences that recruit ribosomes, induce ribosomal assembly, and directly initiate protein translation; (B) Some non-coding RNAs undergo m6A modification, where m6A readers recognize the site. These readers recruit eukaryotic translation initiation factors, thereby promoting peptide translation

Fig. 2

Mechanisms and functions of lncRNA-encoded peptides. (A) The lncRNA-encoded peptides interact with RNA binding proteins, stabilizing their target mRNA molecules; (B) lncRNA-encoded peptides bind target mRNAs, recruit splicing factors, and facilitate the splicing of target genes; (C) lncRNA-encoded peptides bind to transcription factors, promoting their nuclear translocation and regulating the RNA transcription; D, E. lncRNA-encoded peptides influence protein interactions, thereby modulating phosphorylation, ubiquitination, and degradation; F. The lncRNA-encoded peptides localize to mitochondria, impacting mitochondrial function

Fig. 3

Mechanisms and functions of circRNA-encoded peptides. (A) The circRNA-encoded peptides regulate transcription factors activation, thereby controlling the transcription of target genes; (B) These circRNA-encoded peptides bind directly at or competitively inhibit target proteins, affecting their phosphorylation, ubiquitination, and degradation; (C) The circRNA-encoded peptides influence the function of membrane proteins (such as cytokine receptors), thereby modulating downstream signaling pathways